                         SEQUENCE LISTING

<110>  UCL Business Ltd
 
<120>  CHIMERIC ANTIGEN RECEPTOR CELL

<130>  P119492PCT

<150>  GB 2008688.0
<151>  2020-06-09

<160>  18    

<170>  PatentIn version 3.5

<210>  1
<211>  528
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  RQR8-2A-aGFP_GBP6-HNG-CD28TM-41BBZ exemplary sequence

<400>  1

Met Gly Thr Ser Leu Leu Cys Trp Met Ala Leu Cys Leu Leu Gly Ala 
1               5                   10                  15      


Asp His Ala Asp Ala Cys Pro Tyr Ser Asn Pro Ser Leu Cys Ser Gly 
            20                  25                  30          


Gly Gly Gly Ser Glu Leu Pro Thr Gln Gly Thr Phe Ser Asn Val Ser 
        35                  40                  45              


Thr Asn Val Ser Pro Ala Lys Pro Thr Thr Thr Ala Cys Pro Tyr Ser 
    50                  55                  60                  


Asn Pro Ser Leu Cys Ser Gly Gly Gly Gly Ser Pro Ala Pro Arg Pro 
65                  70                  75                  80  


Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro 
                85                  90                  95      


Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu 
            100                 105                 110         


Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys 
        115                 120                 125             


Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Asn His Arg 
    130                 135                 140                 


Asn Arg Arg Arg Val Cys Lys Cys Pro Arg Pro Val Val Arg Ala Glu 
145                 150                 155                 160 


Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu Glu Asn Pro Gly 
                165                 170                 175     


Pro Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val 
            180                 185                 190         


Pro Gly Ser Thr Gly Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Ser 
        195                 200                 205             


Val Gln Thr Gly Gly Ser Leu Arg Leu Ser Cys Ala Val Ser Pro Tyr 
    210                 215                 220                 


Ile Gly Ser Arg Ile Ser Leu Gly Trp Phe Arg Gln Ala Pro Gly Lys 
225                 230                 235                 240 


Val Arg Glu Gly Val Ala Leu Ile Asn Ser Arg Asp Gly Ser Thr Tyr 
                245                 250                 255     


Tyr Ala Asp Thr Val Lys Gly Arg Phe Thr Ile Ser Gln Gly Asp Ala 
            260                 265                 270         


Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala 
        275                 280                 285             


Ile Tyr Tyr Cys Ala Ala Arg Trp Gly Gln Ile Thr Asp Ile Gln Ala 
    290                 295                 300                 


Leu Ala Val Ala Ser Phe Pro Asp Trp Gly Gln Gly Thr Gln Val Thr 
305                 310                 315                 320 


Val Ser Ser Asp Pro Ala Glu Pro Lys Ser Pro Asp Lys Thr His Thr 
                325                 330                 335     


Cys Pro Pro Cys Pro Lys Asp Pro Lys Phe Trp Val Leu Val Val Val 
            340                 345                 350         


Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile 
        355                 360                 365             


Ile Phe Trp Val Arg Ser Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile 
    370                 375                 380                 


Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp 
385                 390                 395                 400 


Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu 
                405                 410                 415     


Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly 
            420                 425                 430         


Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr 
        435                 440                 445             


Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys 
    450                 455                 460                 


Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys 
465                 470                 475                 480 


Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg 
                485                 490                 495     


Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala 
            500                 505                 510         


Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
        515                 520                 525             


<210>  2
<211>  651
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  RQR8-2A-aCD19FMC63_LH-HNG-CD28TM-41BBZ exemplary sequence

<400>  2

Met Gly Thr Ser Leu Leu Cys Trp Met Ala Leu Cys Leu Leu Gly Ala 
1               5                   10                  15      


Asp His Ala Asp Ala Cys Pro Tyr Ser Asn Pro Ser Leu Cys Ser Gly 
            20                  25                  30          


Gly Gly Gly Ser Glu Leu Pro Thr Gln Gly Thr Phe Ser Asn Val Ser 
        35                  40                  45              


Thr Asn Val Ser Pro Ala Lys Pro Thr Thr Thr Ala Cys Pro Tyr Ser 
    50                  55                  60                  


Asn Pro Ser Leu Cys Ser Gly Gly Gly Gly Ser Pro Ala Pro Arg Pro 
65                  70                  75                  80  


Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro 
                85                  90                  95      


Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu 
            100                 105                 110         


Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys 
        115                 120                 125             


Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Asn His Arg 
    130                 135                 140                 


Asn Arg Arg Arg Val Cys Lys Cys Pro Arg Pro Val Val Arg Ala Glu 
145                 150                 155                 160 


Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu Glu Asn Pro Gly 
                165                 170                 175     


Pro Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val 
            180                 185                 190         


Pro Gly Ser Thr Gly Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu 
        195                 200                 205             


Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln 
    210                 215                 220                 


Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr 
225                 230                 235                 240 


Val Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val Pro 
                245                 250                 255     


Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile 
            260                 265                 270         


Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly 
        275                 280                 285             


Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr 
    290                 295                 300                 


Lys Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
305                 310                 315                 320 


Ser Gly Gly Gly Gly Ser Glu Val Lys Leu Gln Glu Ser Gly Pro Gly 
                325                 330                 335     


Leu Val Ala Pro Ser Gln Ser Leu Ser Val Thr Cys Thr Val Ser Gly 
            340                 345                 350         


Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Arg 
        355                 360                 365             


Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr 
    370                 375                 380                 


Tyr Asn Ser Ala Leu Lys Ser Arg Leu Thr Ile Ile Lys Asp Asn Ser 
385                 390                 395                 400 


Lys Ser Gln Val Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp Thr 
                405                 410                 415     


Ala Ile Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala 
            420                 425                 430         


Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Asp Pro 
        435                 440                 445             


Ala Glu Pro Lys Ser Pro Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
    450                 455                 460                 


Lys Asp Pro Lys Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala 
465                 470                 475                 480 


Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Arg 
                485                 490                 495     


Ser Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe 
            500                 505                 510         


Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg 
        515                 520                 525             


Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser 
    530                 535                 540                 


Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr 
545                 550                 555                 560 


Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys 
                565                 570                 575     


Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn 
            580                 585                 590         


Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu 
        595                 600                 605             


Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly 
    610                 615                 620                 


His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr 
625                 630                 635                 640 


Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
                645                 650     


<210>  3
<211>  654
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  RQR8-2A-aCD33glx_LH-HNG-CD28TM-41BBZ exemplary sequence

<400>  3

Met Gly Thr Ser Leu Leu Cys Trp Met Ala Leu Cys Leu Leu Gly Ala 
1               5                   10                  15      


Asp His Ala Asp Ala Cys Pro Tyr Ser Asn Pro Ser Leu Cys Ser Gly 
            20                  25                  30          


Gly Gly Gly Ser Glu Leu Pro Thr Gln Gly Thr Phe Ser Asn Val Ser 
        35                  40                  45              


Thr Asn Val Ser Pro Ala Lys Pro Thr Thr Thr Ala Cys Pro Tyr Ser 
    50                  55                  60                  


Asn Pro Ser Leu Cys Ser Gly Gly Gly Gly Ser Pro Ala Pro Arg Pro 
65                  70                  75                  80  


Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro 
                85                  90                  95      


Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu 
            100                 105                 110         


Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys 
        115                 120                 125             


Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Asn His Arg 
    130                 135                 140                 


Asn Arg Arg Arg Val Cys Lys Cys Pro Arg Pro Val Val Arg Ala Glu 
145                 150                 155                 160 


Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu Glu Asn Pro Gly 
                165                 170                 175     


Pro Met Ala Val Pro Thr Gln Val Leu Gly Leu Leu Leu Leu Trp Leu 
            180                 185                 190         


Thr Asp Ala Arg Cys Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 
        195                 200                 205             


Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu 
    210                 215                 220                 


Asp Ile Tyr Phe Asn Leu Val Trp Tyr Gln Gln Lys Pro Gly Lys Ala 
225                 230                 235                 240 


Pro Lys Leu Leu Ile Tyr Asp Thr Asn Arg Leu Ala Asp Gly Val Pro 
                245                 250                 255     


Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Gln Tyr Thr Leu Thr Ile 
            260                 265                 270         


Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln His Tyr 
        275                 280                 285             


Lys Asn Tyr Pro Leu Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
    290                 295                 300                 


Arg Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
305                 310                 315                 320 


Ser Gly Gly Gly Gly Ser Arg Ser Glu Val Gln Leu Val Glu Ser Gly 
                325                 330                 335     


Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala 
            340                 345                 350         


Ser Gly Phe Thr Leu Ser Asn Tyr Gly Met His Trp Ile Arg Gln Ala 
        355                 360                 365             


Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Leu Asn Gly Gly 
    370                 375                 380                 


Ser Thr Tyr Tyr Arg Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg 
385                 390                 395                 400 


Asp Asn Ala Lys Ser Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala 
                405                 410                 415     


Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala Gln Asp Ala Tyr Thr Gly 
            420                 425                 430         


Gly Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        435                 440                 445             


Met Asp Pro Ala Glu Pro Lys Ser Pro Asp Lys Thr His Thr Cys Pro 
    450                 455                 460                 


Pro Cys Pro Lys Asp Pro Lys Phe Trp Val Leu Val Val Val Gly Gly 
465                 470                 475                 480 


Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe 
                485                 490                 495     


Trp Val Arg Ser Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys 
            500                 505                 510         


Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys 
        515                 520                 525             


Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val 
    530                 535                 540                 


Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn 
545                 550                 555                 560 


Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val 
                565                 570                 575     


Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg 
            580                 585                 590         


Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys 
        595                 600                 605             


Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg 
    610                 615                 620                 


Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys 
625                 630                 635                 640 


Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
                645                 650                 


<210>  4
<211>  963
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  RQR8-2A-aGFP_GBP6-HNG-CD28TM-41BBZ-E2A-aGFP_kub4_VHH-L3-aCD33glx_
       LH-H6 exemplary sequence

<400>  4

Met Gly Thr Ser Leu Leu Cys Trp Met Ala Leu Cys Leu Leu Gly Ala 
1               5                   10                  15      


Asp His Ala Asp Ala Cys Pro Tyr Ser Asn Pro Ser Leu Cys Ser Gly 
            20                  25                  30          


Gly Gly Gly Ser Glu Leu Pro Thr Gln Gly Thr Phe Ser Asn Val Ser 
        35                  40                  45              


Thr Asn Val Ser Pro Ala Lys Pro Thr Thr Thr Ala Cys Pro Tyr Ser 
    50                  55                  60                  


Asn Pro Ser Leu Cys Ser Gly Gly Gly Gly Ser Pro Ala Pro Arg Pro 
65                  70                  75                  80  


Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro 
                85                  90                  95      


Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu 
            100                 105                 110         


Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys 
        115                 120                 125             


Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Asn His Arg 
    130                 135                 140                 


Asn Arg Arg Arg Val Cys Lys Cys Pro Arg Pro Val Val Arg Ala Glu 
145                 150                 155                 160 


Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu Glu Asn Pro Gly 
                165                 170                 175     


Pro Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val 
            180                 185                 190         


Pro Gly Ser Thr Gly Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Ser 
        195                 200                 205             


Val Gln Thr Gly Gly Ser Leu Arg Leu Ser Cys Ala Val Ser Pro Tyr 
    210                 215                 220                 


Ile Gly Ser Arg Ile Ser Leu Gly Trp Phe Arg Gln Ala Pro Gly Lys 
225                 230                 235                 240 


Val Arg Glu Gly Val Ala Leu Ile Asn Ser Arg Asp Gly Ser Thr Tyr 
                245                 250                 255     


Tyr Ala Asp Thr Val Lys Gly Arg Phe Thr Ile Ser Gln Gly Asp Ala 
            260                 265                 270         


Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala 
        275                 280                 285             


Ile Tyr Tyr Cys Ala Ala Arg Trp Gly Gln Ile Thr Asp Ile Gln Ala 
    290                 295                 300                 


Leu Ala Val Ala Ser Phe Pro Asp Trp Gly Gln Gly Thr Gln Val Thr 
305                 310                 315                 320 


Val Ser Ser Asp Pro Ala Glu Pro Lys Ser Pro Asp Lys Thr His Thr 
                325                 330                 335     


Cys Pro Pro Cys Pro Lys Asp Pro Lys Phe Trp Val Leu Val Val Val 
            340                 345                 350         


Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile 
        355                 360                 365             


Ile Phe Trp Val Arg Ser Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile 
    370                 375                 380                 


Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp 
385                 390                 395                 400 


Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu 
                405                 410                 415     


Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly 
            420                 425                 430         


Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr 
        435                 440                 445             


Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys 
    450                 455                 460                 


Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys 
465                 470                 475                 480 


Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg 
                485                 490                 495     


Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala 
            500                 505                 510         


Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
        515                 520                 525             


Gln Cys Thr Asn Tyr Ala Leu Leu Lys Leu Ala Gly Asp Val Glu Ser 
    530                 535                 540                 


Asn Pro Gly Pro Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu 
545                 550                 555                 560 


Ser Leu Ala Leu Val Thr Asn Ser Gln Val Gln Leu Val Glu Ser Gly 
                565                 570                 575     


Gly Ala Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala 
            580                 585                 590         


Ser Gly Phe Pro Val Asn Arg Tyr Ser Met Arg Trp Tyr Arg Gln Ala 
        595                 600                 605             


Pro Gly Lys Glu Arg Glu Trp Val Ala Gly Met Ser Ser Ala Gly Asp 
    610                 615                 620                 


Arg Ser Ser Tyr Glu Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg 
625                 630                 635                 640 


Asp Asp Ala Arg Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro 
                645                 650                 655     


Glu Asp Thr Ala Val Tyr Tyr Cys Asn Val Asn Val Gly Phe Glu Tyr 
            660                 665                 670         


Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Asp Pro Ser Gly Gly 
        675                 680                 685             


Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln 
    690                 695                 700                 


Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val 
705                 710                 715                 720 


Thr Ile Thr Cys Arg Ala Ser Glu Asp Ile Tyr Phe Asn Leu Val Trp 
                725                 730                 735     


Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Asp Thr 
            740                 745                 750         


Asn Arg Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser 
        755                 760                 765             


Gly Thr Gln Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe 
    770                 775                 780                 


Ala Thr Tyr Tyr Cys Gln His Tyr Lys Asn Tyr Pro Leu Thr Phe Gly 
785                 790                 795                 800 


Gln Gly Thr Lys Leu Glu Ile Lys Arg Ser Gly Gly Gly Gly Ser Gly 
                805                 810                 815     


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Ser 
            820                 825                 830         


Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
        835                 840                 845             


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Leu Ser Asn Tyr 
    850                 855                 860                 


Gly Met His Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
865                 870                 875                 880 


Ser Ser Ile Ser Leu Asn Gly Gly Ser Thr Tyr Tyr Arg Asp Ser Val 
                885                 890                 895     


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Ser Thr Leu Tyr 
            900                 905                 910         


Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
        915                 920                 925             


Ala Ala Gln Asp Ala Tyr Thr Gly Gly Tyr Phe Asp Tyr Trp Gly Gln 
    930                 935                 940                 


Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser His His His 
945                 950                 955                 960 


His His His 
            


<210>  5
<211>  957
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  RQR8-2A-aGFP_GBP6-HNG-CD28TM-41BBZ-E2A-aGFP_kub4_VHH-L3-aCD19FMC6
       3_HL-H6 exemplary sequence

<400>  5

Met Gly Thr Ser Leu Leu Cys Trp Met Ala Leu Cys Leu Leu Gly Ala 
1               5                   10                  15      


Asp His Ala Asp Ala Cys Pro Tyr Ser Asn Pro Ser Leu Cys Ser Gly 
            20                  25                  30          


Gly Gly Gly Ser Glu Leu Pro Thr Gln Gly Thr Phe Ser Asn Val Ser 
        35                  40                  45              


Thr Asn Val Ser Pro Ala Lys Pro Thr Thr Thr Ala Cys Pro Tyr Ser 
    50                  55                  60                  


Asn Pro Ser Leu Cys Ser Gly Gly Gly Gly Ser Pro Ala Pro Arg Pro 
65                  70                  75                  80  


Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro 
                85                  90                  95      


Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu 
            100                 105                 110         


Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys 
        115                 120                 125             


Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Asn His Arg 
    130                 135                 140                 


Asn Arg Arg Arg Val Cys Lys Cys Pro Arg Pro Val Val Arg Ala Glu 
145                 150                 155                 160 


Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu Glu Asn Pro Gly 
                165                 170                 175     


Pro Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val 
            180                 185                 190         


Pro Gly Ser Thr Gly Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Ser 
        195                 200                 205             


Val Gln Thr Gly Gly Ser Leu Arg Leu Ser Cys Ala Val Ser Pro Tyr 
    210                 215                 220                 


Ile Gly Ser Arg Ile Ser Leu Gly Trp Phe Arg Gln Ala Pro Gly Lys 
225                 230                 235                 240 


Val Arg Glu Gly Val Ala Leu Ile Asn Ser Arg Asp Gly Ser Thr Tyr 
                245                 250                 255     


Tyr Ala Asp Thr Val Lys Gly Arg Phe Thr Ile Ser Gln Gly Asp Ala 
            260                 265                 270         


Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala 
        275                 280                 285             


Ile Tyr Tyr Cys Ala Ala Arg Trp Gly Gln Ile Thr Asp Ile Gln Ala 
    290                 295                 300                 


Leu Ala Val Ala Ser Phe Pro Asp Trp Gly Gln Gly Thr Gln Val Thr 
305                 310                 315                 320 


Val Ser Ser Asp Pro Ala Glu Pro Lys Ser Pro Asp Lys Thr His Thr 
                325                 330                 335     


Cys Pro Pro Cys Pro Lys Asp Pro Lys Phe Trp Val Leu Val Val Val 
            340                 345                 350         


Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile 
        355                 360                 365             


Ile Phe Trp Val Arg Ser Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile 
    370                 375                 380                 


Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp 
385                 390                 395                 400 


Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu 
                405                 410                 415     


Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly 
            420                 425                 430         


Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr 
        435                 440                 445             


Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys 
    450                 455                 460                 


Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys 
465                 470                 475                 480 


Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg 
                485                 490                 495     


Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala 
            500                 505                 510         


Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
        515                 520                 525             


Gln Cys Thr Asn Tyr Ala Leu Leu Lys Leu Ala Gly Asp Val Glu Ser 
    530                 535                 540                 


Asn Pro Gly Pro Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu 
545                 550                 555                 560 


Ser Leu Ala Leu Val Thr Asn Ser Gln Val Gln Leu Val Glu Ser Gly 
                565                 570                 575     


Gly Ala Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala 
            580                 585                 590         


Ser Gly Phe Pro Val Asn Arg Tyr Ser Met Arg Trp Tyr Arg Gln Ala 
        595                 600                 605             


Pro Gly Lys Glu Arg Glu Trp Val Ala Gly Met Ser Ser Ala Gly Asp 
    610                 615                 620                 


Arg Ser Ser Tyr Glu Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg 
625                 630                 635                 640 


Asp Asp Ala Arg Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro 
                645                 650                 655     


Glu Asp Thr Ala Val Tyr Tyr Cys Asn Val Asn Val Gly Phe Glu Tyr 
            660                 665                 670         


Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Asp Pro Ser Gly Gly 
        675                 680                 685             


Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Lys 
    690                 695                 700                 


Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser 
705                 710                 715                 720 


Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser 
                725                 730                 735     


Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile 
            740                 745                 750         


Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu 
        755                 760                 765             


Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn 
    770                 775                 780                 


Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr 
785                 790                 795                 800 


Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser 
                805                 810                 815     


Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
            820                 825                 830         


Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser 
        835                 840                 845             


Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp 
    850                 855                 860                 


Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val 
865                 870                 875                 880 


Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser 
                885                 890                 895     


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser 
            900                 905                 910         


Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn 
        915                 920                 925             


Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Lys 
    930                 935                 940                 


Ala Ser Gly Gly Gly Gly Ser His His His His His His 
945                 950                 955         


<210>  6
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  signal peptide

<400>  6

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


Gly Ser Thr Gly 
            20  


<210>  7
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker peptide

<400>  7

Ser Gly Gly Gly Gly 
1               5   


<210>  8
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker peptide

<400>  8

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10                  15      


<210>  9
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  XTEN linker peptide

<400>  9

Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser 
1               5                   10                  15      


<210>  10
<211>  415
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  aGFP_kub4_VHH-L3-aCD33glx_LH-H6 bi-specific protein

<400>  10

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


Gly Ser Thr Gly Gln Val Gln Leu Val Glu Ser Gly Gly Ala Leu Val 
            20                  25                  30          


Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Pro 
        35                  40                  45              


Val Asn Arg Tyr Ser Met Arg Trp Tyr Arg Gln Ala Pro Gly Lys Glu 
    50                  55                  60                  


Arg Glu Trp Val Ala Gly Met Ser Ser Ala Gly Asp Arg Ser Ser Tyr 
65                  70                  75                  80  


Glu Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ala Arg 
                85                  90                  95      


Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala 
            100                 105                 110         


Val Tyr Tyr Cys Asn Val Asn Val Gly Phe Glu Tyr Trp Gly Gln Gly 
        115                 120                 125             


Thr Gln Val Thr Val Ser Ser Asp Pro Ser Gly Gly Gly Gly Ser Gly 
    130                 135                 140                 


Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser 
145                 150                 155                 160 


Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys 
                165                 170                 175     


Arg Ala Ser Glu Asp Ile Tyr Phe Asn Leu Val Trp Tyr Gln Gln Lys 
            180                 185                 190         


Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Asp Thr Asn Arg Leu Ala 
        195                 200                 205             


Asp Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Gln Tyr 
    210                 215                 220                 


Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 
225                 230                 235                 240 


Cys Gln His Tyr Lys Asn Tyr Pro Leu Thr Phe Gly Gln Gly Thr Lys 
                245                 250                 255     


Leu Glu Ile Lys Arg Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
            260                 265                 270         


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Ser Glu Val Gln Leu 
        275                 280                 285             


Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu 
    290                 295                 300                 


Ser Cys Ala Ala Ser Gly Phe Thr Leu Ser Asn Tyr Gly Met His Trp 
305                 310                 315                 320 


Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser 
                325                 330                 335     


Leu Asn Gly Gly Ser Thr Tyr Tyr Arg Asp Ser Val Lys Gly Arg Phe 
            340                 345                 350         


Thr Ile Ser Arg Asp Asn Ala Lys Ser Thr Leu Tyr Leu Gln Met Asn 
        355                 360                 365             


Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala Gln Asp 
    370                 375                 380                 


Ala Tyr Thr Gly Gly Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 
385                 390                 395                 400 


Thr Val Ser Ser Gly Gly Gly Gly Ser His His His His His His 
                405                 410                 415 


<210>  11
<211>  409
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  aGFP_kub4_VHH-L3-aCD19FMC63_HL-H6 bi-specific protein

<400>  11

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


Gly Ser Thr Gly Gln Val Gln Leu Val Glu Ser Gly Gly Ala Leu Val 
            20                  25                  30          


Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Pro 
        35                  40                  45              


Val Asn Arg Tyr Ser Met Arg Trp Tyr Arg Gln Ala Pro Gly Lys Glu 
    50                  55                  60                  


Arg Glu Trp Val Ala Gly Met Ser Ser Ala Gly Asp Arg Ser Ser Tyr 
65                  70                  75                  80  


Glu Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ala Arg 
                85                  90                  95      


Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala 
            100                 105                 110         


Val Tyr Tyr Cys Asn Val Asn Val Gly Phe Glu Tyr Trp Gly Gln Gly 
        115                 120                 125             


Thr Gln Val Thr Val Ser Ser Asp Pro Ser Gly Gly Gly Gly Ser Gly 
    130                 135                 140                 


Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Lys Leu Gln Glu Ser 
145                 150                 155                 160 


Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser Val Thr Cys Thr 
                165                 170                 175     


Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln 
            180                 185                 190         


Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Gly Ser Glu 
        195                 200                 205             


Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu Thr Ile Ile Lys 
    210                 215                 220                 


Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn Ser Leu Gln Thr 
225                 230                 235                 240 


Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly 
                245                 250                 255     


Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser 
            260                 265                 270         


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        275                 280                 285             


Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly 
    290                 295                 300                 


Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 
305                 310                 315                 320 


Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile 
                325                 330                 335     


Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 
            340                 345                 350         


Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln 
        355                 360                 365             


Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr 
    370                 375                 380                 


Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Lys Ala Ser Gly Gly 
385                 390                 395                 400 


Gly Gly Ser His His His His His His 
                405                 


<210>  12
<211>  285
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  intracellular 3xMYC-XTEN_L-eGFP

<400>  12

Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser 
1               5                   10                  15      


Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Ser Gly 
            20                  25                  30          


Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met Val 
        35                  40                  45              


Ser Lys Gly Glu Glu Leu Phe Thr Gly Val Val Pro Ile Leu Val Glu 
    50                  55                  60                  


Leu Asp Gly Asp Val Asn Gly His Lys Phe Ser Val Ser Gly Glu Gly 
65                  70                  75                  80  


Glu Gly Asp Ala Thr Tyr Gly Lys Leu Thr Leu Lys Phe Ile Cys Thr 
                85                  90                  95      


Thr Gly Lys Leu Pro Val Pro Trp Pro Thr Leu Val Thr Thr Leu Thr 
            100                 105                 110         


Tyr Gly Val Gln Cys Phe Ser Arg Tyr Pro Asp His Met Lys Gln His 
        115                 120                 125             


Asp Phe Phe Lys Ser Ala Met Pro Glu Gly Tyr Val Gln Glu Arg Thr 
    130                 135                 140                 


Ile Phe Phe Lys Asp Asp Gly Asn Tyr Lys Thr Arg Ala Glu Val Lys 
145                 150                 155                 160 


Phe Glu Gly Asp Thr Leu Val Asn Arg Ile Glu Leu Lys Gly Ile Asp 
                165                 170                 175     


Phe Lys Glu Asp Gly Asn Ile Leu Gly His Lys Leu Glu Tyr Asn Tyr 
            180                 185                 190         


Asn Ser His Asn Val Tyr Ile Met Ala Asp Lys Gln Lys Asn Gly Ile 
        195                 200                 205             


Lys Val Asn Phe Lys Ile Arg His Asn Ile Glu Asp Gly Ser Val Gln 
    210                 215                 220                 


Leu Ala Asp His Tyr Gln Gln Asn Thr Pro Ile Gly Asp Gly Pro Val 
225                 230                 235                 240 


Leu Leu Pro Asp Asn His Tyr Leu Ser Thr Gln Ser Ala Leu Ser Lys 
                245                 250                 255     


Asp Pro Asn Glu Lys Arg Asp His Met Val Leu Leu Glu Phe Val Thr 
            260                 265                 270         


Ala Ala Gly Ile Thr Leu Gly Met Asp Glu Leu Tyr Lys 
        275                 280                 285 


<210>  13
<211>  2316
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  p210_BCR-ABL-3xMYC-XTEN_L-eGFP

<400>  13

Met Val Asp Pro Val Gly Phe Ala Glu Ala Trp Lys Ala Gln Phe Pro 
1               5                   10                  15      


Asp Ser Glu Pro Pro Arg Met Glu Leu Arg Ser Val Gly Asp Ile Glu 
            20                  25                  30          


Gln Glu Leu Glu Arg Cys Lys Ala Ser Ile Arg Arg Leu Glu Gln Glu 
        35                  40                  45              


Val Asn Gln Glu Arg Phe Arg Met Ile Tyr Leu Gln Thr Leu Leu Ala 
    50                  55                  60                  


Lys Glu Lys Lys Ser Tyr Asp Arg Gln Arg Trp Gly Phe Arg Arg Ala 
65                  70                  75                  80  


Ala Gln Ala Pro Asp Gly Ala Ser Glu Pro Arg Ala Ser Ala Ser Arg 
                85                  90                  95      


Pro Gln Pro Ala Pro Ala Asp Gly Ala Asp Pro Pro Pro Ala Glu Glu 
            100                 105                 110         


Pro Glu Ala Arg Pro Asp Gly Glu Gly Ser Pro Gly Lys Ala Arg Pro 
        115                 120                 125             


Gly Thr Ala Arg Arg Pro Gly Ala Ala Ala Ser Gly Glu Arg Asp Asp 
    130                 135                 140                 


Arg Gly Pro Pro Ala Ser Val Ala Ala Leu Arg Ser Asn Phe Glu Arg 
145                 150                 155                 160 


Ile Arg Lys Gly His Gly Gln Pro Gly Ala Asp Ala Glu Lys Pro Phe 
                165                 170                 175     


Tyr Val Asn Val Glu Phe His His Glu Arg Gly Leu Val Lys Val Asn 
            180                 185                 190         


Asp Lys Glu Val Ser Asp Arg Ile Ser Ser Leu Gly Ser Gln Ala Met 
        195                 200                 205             


Gln Met Glu Arg Lys Lys Ser Gln His Gly Ala Gly Ser Ser Val Gly 
    210                 215                 220                 


Asp Ala Ser Arg Pro Pro Tyr Arg Gly Arg Ser Ser Glu Ser Ser Cys 
225                 230                 235                 240 


Gly Val Asp Gly Asp Tyr Glu Asp Ala Glu Leu Asn Pro Arg Phe Leu 
                245                 250                 255     


Lys Asp Asn Leu Ile Asp Ala Asn Gly Gly Ser Arg Pro Pro Trp Pro 
            260                 265                 270         


Pro Leu Glu Tyr Gln Pro Tyr Gln Ser Ile Tyr Val Gly Gly Met Met 
        275                 280                 285             


Glu Gly Glu Gly Lys Gly Pro Leu Leu Arg Ser Gln Ser Thr Ser Glu 
    290                 295                 300                 


Gln Glu Lys Arg Leu Thr Trp Pro Arg Arg Ser Tyr Ser Pro Arg Ser 
305                 310                 315                 320 


Phe Glu Asp Cys Gly Gly Gly Tyr Thr Pro Asp Cys Ser Ser Asn Glu 
                325                 330                 335     


Asn Leu Thr Ser Ser Glu Glu Asp Phe Ser Ser Gly Gln Ser Ser Arg 
            340                 345                 350         


Val Ser Pro Ser Pro Thr Thr Tyr Arg Met Phe Arg Asp Lys Ser Arg 
        355                 360                 365             


Ser Pro Ser Gln Asn Ser Gln Gln Ser Phe Asp Ser Ser Ser Pro Pro 
    370                 375                 380                 


Thr Pro Gln Cys His Lys Arg His Arg His Cys Pro Val Val Val Ser 
385                 390                 395                 400 


Glu Ala Thr Ile Val Gly Val Arg Lys Thr Gly Gln Ile Trp Pro Asn 
                405                 410                 415     


Asp Gly Glu Gly Ala Phe His Gly Asp Ala Asp Gly Ser Phe Gly Thr 
            420                 425                 430         


Pro Pro Gly Tyr Gly Cys Ala Ala Asp Arg Ala Glu Glu Gln Arg Arg 
        435                 440                 445             


His Gln Asp Gly Leu Pro Tyr Ile Asp Asp Ser Pro Ser Ser Ser Pro 
    450                 455                 460                 


His Leu Ser Ser Lys Gly Arg Gly Ser Arg Asp Ala Leu Val Ser Gly 
465                 470                 475                 480 


Ala Leu Glu Ser Thr Lys Ala Ser Glu Leu Asp Leu Glu Lys Gly Leu 
                485                 490                 495     


Glu Met Arg Lys Trp Val Leu Ser Gly Ile Leu Ala Ser Glu Glu Thr 
            500                 505                 510         


Tyr Leu Ser His Leu Glu Ala Leu Leu Leu Pro Met Lys Pro Leu Lys 
        515                 520                 525             


Ala Ala Ala Thr Thr Ser Gln Pro Val Leu Thr Ser Gln Gln Ile Glu 
    530                 535                 540                 


Thr Ile Phe Phe Lys Val Pro Glu Leu Tyr Glu Ile His Lys Glu Phe 
545                 550                 555                 560 


Tyr Asp Gly Leu Phe Pro Arg Val Gln Gln Trp Ser His Gln Gln Arg 
                565                 570                 575     


Val Gly Asp Leu Phe Gln Lys Leu Ala Ser Gln Leu Gly Val Tyr Arg 
            580                 585                 590         


Ala Phe Val Asp Asn Tyr Gly Val Ala Met Glu Met Ala Glu Lys Cys 
        595                 600                 605             


Cys Gln Ala Asn Ala Gln Phe Ala Glu Ile Ser Glu Asn Leu Arg Ala 
    610                 615                 620                 


Arg Ser Asn Lys Asp Ala Lys Asp Pro Thr Thr Lys Asn Ser Leu Glu 
625                 630                 635                 640 


Thr Leu Leu Tyr Lys Pro Val Asp Arg Val Thr Arg Ser Thr Leu Val 
                645                 650                 655     


Leu His Asp Leu Leu Lys His Thr Pro Ala Ser His Pro Asp His Pro 
            660                 665                 670         


Leu Leu Gln Asp Ala Leu Arg Ile Ser Gln Asn Phe Leu Ser Ser Ile 
        675                 680                 685             


Asn Glu Glu Ile Thr Pro Arg Arg Gln Ser Met Thr Val Lys Lys Gly 
    690                 695                 700                 


Glu His Arg Gln Leu Leu Lys Asp Ser Phe Met Val Glu Leu Val Glu 
705                 710                 715                 720 


Gly Ala Arg Lys Leu Arg His Val Phe Leu Phe Thr Asp Leu Leu Leu 
                725                 730                 735     


Cys Thr Lys Leu Lys Lys Gln Ser Gly Gly Lys Thr Gln Gln Tyr Asp 
            740                 745                 750         


Cys Lys Trp Tyr Ile Pro Leu Thr Asp Leu Ser Phe Gln Met Val Asp 
        755                 760                 765             


Glu Leu Glu Ala Val Pro Asn Ile Pro Leu Val Pro Asp Glu Glu Leu 
    770                 775                 780                 


Asp Ala Leu Lys Ile Lys Ile Ser Gln Ile Lys Ser Asp Ile Gln Arg 
785                 790                 795                 800 


Glu Lys Arg Ala Asn Lys Gly Ser Lys Ala Thr Glu Arg Leu Lys Lys 
                805                 810                 815     


Lys Leu Ser Glu Gln Glu Ser Leu Leu Leu Leu Met Ser Pro Ser Met 
            820                 825                 830         


Ala Phe Arg Val His Ser Arg Asn Gly Lys Ser Tyr Thr Phe Leu Ile 
        835                 840                 845             


Ser Ser Asp Tyr Glu Arg Ala Glu Trp Arg Glu Asn Ile Arg Glu Gln 
    850                 855                 860                 


Gln Lys Lys Cys Phe Arg Ser Phe Ser Leu Thr Ser Val Glu Leu Gln 
865                 870                 875                 880 


Met Leu Thr Asn Ser Cys Val Lys Leu Gln Thr Val His Ser Ile Pro 
                885                 890                 895     


Leu Thr Ile Asn Lys Glu Asp Asp Glu Ser Pro Gly Leu Tyr Gly Phe 
            900                 905                 910         


Leu Asn Val Ile Val His Ser Ala Thr Gly Phe Lys Gln Ser Ser Lys 
        915                 920                 925             


Ala Leu Gln Arg Pro Val Ala Ser Asp Phe Glu Pro Gln Gly Leu Ser 
    930                 935                 940                 


Glu Ala Ala Arg Trp Asn Ser Lys Glu Asn Leu Leu Ala Gly Pro Ser 
945                 950                 955                 960 


Glu Asn Asp Pro Asn Leu Phe Val Ala Leu Tyr Asp Phe Val Ala Ser 
                965                 970                 975     


Gly Asp Asn Thr Leu Ser Ile Thr Lys Gly Glu Lys Leu Arg Val Leu 
            980                 985                 990         


Gly Tyr Asn His Asn Gly Glu Trp  Cys Glu Ala Gln Thr  Lys Asn Gly 
        995                 1000                 1005             


Gln Gly  Trp Val Pro Ser Asn  Tyr Ile Thr Pro Val  Asn Ser Leu 
    1010                 1015                 1020             


Glu Lys  His Ser Trp Tyr His  Gly Pro Val Ser Arg  Asn Ala Ala 
    1025                 1030                 1035             


Glu Tyr  Leu Leu Ser Ser Gly  Ile Asn Gly Ser Phe  Leu Val Arg 
    1040                 1045                 1050             


Glu Ser  Glu Ser Ser Pro Gly  Gln Arg Ser Ile Ser  Leu Arg Tyr 
    1055                 1060                 1065             


Glu Gly  Arg Val Tyr His Tyr  Arg Ile Asn Thr Ala  Ser Asp Gly 
    1070                 1075                 1080             


Lys Leu  Tyr Val Ser Ser Glu  Ser Arg Phe Asn Thr  Leu Ala Glu 
    1085                 1090                 1095             


Leu Val  His His His Ser Thr  Val Ala Asp Gly Leu  Ile Thr Thr 
    1100                 1105                 1110             


Leu His  Tyr Pro Ala Pro Lys  Arg Asn Lys Pro Thr  Val Tyr Gly 
    1115                 1120                 1125             


Val Ser  Pro Asn Tyr Asp Lys  Trp Glu Met Glu Arg  Thr Asp Ile 
    1130                 1135                 1140             


Thr Met  Lys His Lys Leu Gly  Gly Gly Gln Tyr Gly  Glu Val Tyr 
    1145                 1150                 1155             


Glu Gly  Val Trp Lys Lys Tyr  Ser Leu Thr Val Ala  Val Lys Thr 
    1160                 1165                 1170             


Leu Lys  Glu Asp Thr Met Glu  Val Glu Glu Phe Leu  Lys Glu Ala 
    1175                 1180                 1185             


Ala Val  Met Lys Glu Ile Lys  His Pro Asn Leu Val  Gln Leu Leu 
    1190                 1195                 1200             


Gly Val  Cys Thr Arg Glu Pro  Pro Phe Tyr Ile Ile  Thr Glu Phe 
    1205                 1210                 1215             


Met Thr  Tyr Gly Asn Leu Leu  Asp Tyr Leu Arg Glu  Cys Asn Arg 
    1220                 1225                 1230             


Gln Glu  Val Asn Ala Val Val  Leu Leu Tyr Met Ala  Thr Gln Ile 
    1235                 1240                 1245             


Ser Ser  Ala Met Glu Tyr Leu  Glu Lys Lys Asn Phe  Ile His Arg 
    1250                 1255                 1260             


Asp Leu  Ala Ala Arg Asn Cys  Leu Val Gly Glu Asn  His Leu Val 
    1265                 1270                 1275             


Lys Val  Ala Asp Phe Gly Leu  Ser Arg Leu Met Thr  Gly Asp Thr 
    1280                 1285                 1290             


Tyr Thr  Ala His Ala Gly Ala  Lys Phe Pro Ile Lys  Trp Thr Ala 
    1295                 1300                 1305             


Pro Glu  Ser Leu Ala Tyr Asn  Lys Phe Ser Ile Lys  Ser Asp Val 
    1310                 1315                 1320             


Trp Ala  Phe Gly Val Leu Leu  Trp Glu Ile Ala Thr  Tyr Gly Met 
    1325                 1330                 1335             


Ser Pro  Tyr Pro Gly Ile Asp  Leu Ser Gln Val Tyr  Glu Leu Leu 
    1340                 1345                 1350             


Glu Lys  Asp Tyr Arg Met Glu  Arg Pro Glu Gly Cys  Pro Glu Lys 
    1355                 1360                 1365             


Val Tyr  Glu Leu Met Arg Ala  Cys Trp Gln Trp Asn  Pro Ser Asp 
    1370                 1375                 1380             


Arg Pro  Ser Phe Ala Glu Ile  His Gln Ala Phe Glu  Thr Met Phe 
    1385                 1390                 1395             


Gln Glu  Ser Ser Ile Ser Asp  Glu Val Glu Lys Glu  Leu Gly Lys 
    1400                 1405                 1410             


Gln Gly  Val Arg Gly Ala Val  Ser Thr Leu Leu Gln  Ala Pro Glu 
    1415                 1420                 1425             


Leu Pro  Thr Lys Thr Arg Thr  Ser Arg Arg Ala Ala  Glu His Arg 
    1430                 1435                 1440             


Asp Thr  Thr Asp Val Pro Glu  Met Pro His Ser Lys  Gly Gln Gly 
    1445                 1450                 1455             


Glu Ser  Asp Pro Leu Asp His  Glu Pro Ala Val Ser  Pro Leu Leu 
    1460                 1465                 1470             


Pro Arg  Lys Glu Arg Gly Pro  Pro Glu Gly Gly Leu  Asn Glu Asp 
    1475                 1480                 1485             


Glu Arg  Leu Leu Pro Lys Asp  Lys Lys Thr Asn Leu  Phe Ser Ala 
    1490                 1495                 1500             


Leu Ile  Lys Lys Lys Lys Lys  Thr Ala Pro Thr Pro  Pro Lys Arg 
    1505                 1510                 1515             


Ser Ser  Ser Phe Arg Glu Met  Asp Gly Gln Pro Glu  Arg Arg Gly 
    1520                 1525                 1530             


Ala Gly  Glu Glu Glu Gly Arg  Asp Ile Ser Asn Gly  Ala Leu Ala 
    1535                 1540                 1545             


Phe Thr  Pro Leu Asp Thr Ala  Asp Pro Ala Lys Ser  Pro Lys Pro 
    1550                 1555                 1560             


Ser Asn  Gly Ala Gly Val Pro  Asn Gly Ala Leu Arg  Glu Ser Gly 
    1565                 1570                 1575             


Gly Ser  Gly Phe Arg Ser Pro  His Leu Trp Lys Lys  Ser Ser Thr 
    1580                 1585                 1590             


Leu Thr  Ser Ser Arg Leu Ala  Thr Gly Glu Glu Glu  Gly Gly Gly 
    1595                 1600                 1605             


Ser Ser  Ser Lys Arg Phe Leu  Arg Ser Cys Ser Ala  Ser Cys Val 
    1610                 1615                 1620             


Pro His  Gly Ala Lys Asp Thr  Glu Trp Arg Ser Val  Thr Leu Pro 
    1625                 1630                 1635             


Arg Asp  Leu Gln Ser Thr Gly  Arg Gln Phe Asp Ser  Ser Thr Phe 
    1640                 1645                 1650             


Gly Gly  His Lys Ser Glu Lys  Pro Ala Leu Pro Arg  Lys Arg Ala 
    1655                 1660                 1665             


Gly Glu  Asn Arg Ser Asp Gln  Val Thr Arg Gly Thr  Val Thr Pro 
    1670                 1675                 1680             


Pro Pro  Arg Leu Val Lys Lys  Asn Glu Glu Ala Ala  Asp Glu Val 
    1685                 1690                 1695             


Phe Lys  Asp Ile Met Glu Ser  Ser Pro Gly Ser Ser  Pro Pro Asn 
    1700                 1705                 1710             


Leu Thr  Pro Lys Pro Leu Arg  Arg Gln Val Thr Val  Ala Pro Ala 
    1715                 1720                 1725             


Ser Gly  Leu Pro His Lys Glu  Glu Ala Gly Lys Gly  Ser Ala Leu 
    1730                 1735                 1740             


Gly Thr  Pro Ala Ala Ala Glu  Pro Val Thr Pro Thr  Ser Lys Ala 
    1745                 1750                 1755             


Gly Ser  Gly Ala Pro Gly Gly  Thr Ser Lys Gly Pro  Ala Glu Glu 
    1760                 1765                 1770             


Ser Arg  Val Arg Arg His Lys  His Ser Ser Glu Ser  Pro Gly Arg 
    1775                 1780                 1785             


Asp Lys  Gly Lys Leu Ser Arg  Leu Lys Pro Ala Pro  Pro Pro Pro 
    1790                 1795                 1800             


Pro Ala  Ala Ser Ala Gly Lys  Ala Gly Gly Lys Pro  Ser Gln Ser 
    1805                 1810                 1815             


Pro Ser  Gln Glu Ala Ala Gly  Glu Ala Val Leu Gly  Ala Lys Thr 
    1820                 1825                 1830             


Lys Ala  Thr Ser Leu Val Asp  Ala Val Asn Ser Asp  Ala Ala Lys 
    1835                 1840                 1845             


Pro Ser  Gln Pro Gly Glu Gly  Leu Lys Lys Pro Val  Leu Pro Ala 
    1850                 1855                 1860             


Thr Pro  Lys Pro Gln Ser Ala  Lys Pro Ser Gly Thr  Pro Ile Ser 
    1865                 1870                 1875             


Pro Ala  Pro Val Pro Ser Thr  Leu Pro Ser Ala Ser  Ser Ala Leu 
    1880                 1885                 1890             


Ala Gly  Asp Gln Pro Ser Ser  Thr Ala Phe Ile Pro  Leu Ile Ser 
    1895                 1900                 1905             


Thr Arg  Val Ser Leu Arg Lys  Thr Arg Gln Pro Pro  Glu Arg Ile 
    1910                 1915                 1920             


Ala Ser  Gly Ala Ile Thr Lys  Gly Val Val Leu Asp  Ser Thr Glu 
    1925                 1930                 1935             


Ala Leu  Cys Leu Ala Ile Ser  Arg Asn Ser Glu Gln  Met Ala Ser 
    1940                 1945                 1950             


His Ser  Ala Val Leu Glu Ala  Gly Lys Asn Leu Tyr  Ser Phe Cys 
    1955                 1960                 1965             


Val Ser  Tyr Val Asp Ser Ile  Gln Gln Met Arg Asn  Lys Phe Ala 
    1970                 1975                 1980             


Phe Arg  Glu Ala Ile Asn Lys  Leu Glu Asn Asn Leu  Arg Glu Leu 
    1985                 1990                 1995             


Gln Ile  Cys Pro Ala Thr Ala  Gly Ser Gly Pro Ala  Ala Thr Gln 
    2000                 2005                 2010             


Asp Phe  Ser Lys Leu Leu Ser  Ser Val Lys Glu Ile  Ser Asp Ile 
    2015                 2020                 2025             


Val Gln  Arg Glu Gln Lys Leu  Ile Ser Glu Glu Asp  Leu Glu Gln 
    2030                 2035                 2040             


Lys Leu  Ile Ser Glu Glu Asp  Leu Glu Gln Lys Leu  Ile Ser Glu 
    2045                 2050                 2055             


Glu Asp  Leu Ser Gly Ser Glu  Thr Pro Gly Thr Ser  Glu Ser Ala 
    2060                 2065                 2070             


Thr Pro  Glu Ser Met Val Ser  Lys Gly Glu Glu Leu  Phe Thr Gly 
    2075                 2080                 2085             


Val Val  Pro Ile Leu Val Glu  Leu Asp Gly Asp Val  Asn Gly His 
    2090                 2095                 2100             


Lys Phe  Ser Val Ser Gly Glu  Gly Glu Gly Asp Ala  Thr Tyr Gly 
    2105                 2110                 2115             


Lys Leu  Thr Leu Lys Phe Ile  Cys Thr Thr Gly Lys  Leu Pro Val 
    2120                 2125                 2130             


Pro Trp  Pro Thr Leu Val Thr  Thr Leu Thr Tyr Gly  Val Gln Cys 
    2135                 2140                 2145             


Phe Ser  Arg Tyr Pro Asp His  Met Lys Gln His Asp  Phe Phe Lys 
    2150                 2155                 2160             


Ser Ala  Met Pro Glu Gly Tyr  Val Gln Glu Arg Thr  Ile Phe Phe 
    2165                 2170                 2175             


Lys Asp  Asp Gly Asn Tyr Lys  Thr Arg Ala Glu Val  Lys Phe Glu 
    2180                 2185                 2190             


Gly Asp  Thr Leu Val Asn Arg  Ile Glu Leu Lys Gly  Ile Asp Phe 
    2195                 2200                 2205             


Lys Glu  Asp Gly Asn Ile Leu  Gly His Lys Leu Glu  Tyr Asn Tyr 
    2210                 2215                 2220             


Asn Ser  His Asn Val Tyr Ile  Met Ala Asp Lys Gln  Lys Asn Gly 
    2225                 2230                 2235             


Ile Lys  Val Asn Phe Lys Ile  Arg His Asn Ile Glu  Asp Gly Ser 
    2240                 2245                 2250             


Val Gln  Leu Ala Asp His Tyr  Gln Gln Asn Thr Pro  Ile Gly Asp 
    2255                 2260                 2265             


Gly Pro  Val Leu Leu Pro Asp  Asn His Tyr Leu Ser  Thr Gln Ser 
    2270                 2275                 2280             


Ala Leu  Ser Lys Asp Pro Asn  Glu Lys Arg Asp His  Met Val Leu 
    2285                 2290                 2295             


Leu Glu  Phe Val Thr Ala Ala  Gly Ile Thr Leu Gly  Met Asp Glu 
    2300                 2305                 2310             


Leu Tyr  Lys 
    2315     


<210>  14
<211>  651
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  RQR8-2A-aEpCAM_MT110_LH-HNG-CD28TM-41BBZ exemplary sequence

<400>  14

Met Gly Thr Ser Leu Leu Cys Trp Met Ala Leu Cys Leu Leu Gly Ala 
1               5                   10                  15      


Asp His Ala Asp Ala Cys Pro Tyr Ser Asn Pro Ser Leu Cys Ser Gly 
            20                  25                  30          


Gly Gly Gly Ser Glu Leu Pro Thr Gln Gly Thr Phe Ser Asn Val Ser 
        35                  40                  45              


Thr Asn Val Ser Pro Ala Lys Pro Thr Thr Thr Ala Cys Pro Tyr Ser 
    50                  55                  60                  


Asn Pro Ser Leu Cys Ser Gly Gly Gly Gly Ser Pro Ala Pro Arg Pro 
65                  70                  75                  80  


Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro 
                85                  90                  95      


Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu 
            100                 105                 110         


Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys 
        115                 120                 125             


Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Asn His Arg 
    130                 135                 140                 


Asn Arg Arg Arg Val Cys Lys Cys Pro Arg Pro Val Val Arg Ala Glu 
145                 150                 155                 160 


Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu Glu Asn Pro Gly 
                165                 170                 175     


Pro Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val 
            180                 185                 190         


Pro Gly Ser Thr Gly Glu Leu Val Met Thr Gln Ser Pro Ser Ser Leu 
        195                 200                 205             


Thr Val Thr Ala Gly Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln 
    210                 215                 220                 


Ser Leu Leu Asn Ser Gly Asn Gln Lys Asn Tyr Leu Thr Trp Tyr Gln 
225                 230                 235                 240 


Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr 
                245                 250                 255     


Arg Glu Ser Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr 
            260                 265                 270         


Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Val 
        275                 280                 285             


Tyr Tyr Cys Gln Asn Asp Tyr Ser Tyr Pro Leu Thr Phe Gly Ala Gly 
    290                 295                 300                 


Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
305                 310                 315                 320 


Gly Gly Gly Gly Ser Glu Val Gln Leu Leu Glu Gln Ser Gly Ala Glu 
                325                 330                 335     


Leu Val Arg Pro Gly Thr Ser Val Lys Ile Ser Cys Lys Ala Ser Gly 
            340                 345                 350         


Tyr Ala Phe Thr Asn Tyr Trp Leu Gly Trp Val Lys Gln Arg Pro Gly 
        355                 360                 365             


His Gly Leu Glu Trp Ile Gly Asp Ile Phe Pro Gly Ser Gly Asn Ile 
    370                 375                 380                 


His Tyr Asn Glu Lys Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys 
385                 390                 395                 400 


Ser Ser Ser Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Phe Glu Asp 
                405                 410                 415     


Ser Ala Val Tyr Phe Cys Ala Arg Leu Arg Asn Trp Asp Glu Pro Met 
            420                 425                 430         


Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ser Asp Pro 
        435                 440                 445             


Ala Glu Pro Lys Ser Pro Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
    450                 455                 460                 


Lys Asp Pro Lys Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala 
465                 470                 475                 480 


Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Arg 
                485                 490                 495     


Ser Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe 
            500                 505                 510         


Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg 
        515                 520                 525             


Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser 
    530                 535                 540                 


Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr 
545                 550                 555                 560 


Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys 
                565                 570                 575     


Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn 
            580                 585                 590         


Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu 
        595                 600                 605             


Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly 
    610                 615                 620                 


His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr 
625                 630                 635                 640 


Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
                645                 650     


<210>  15
<211>  1196
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  RQR8-2A-aP53_421_LH-HNG-CD28TM-41BBZ-E2A-aEpCAM_MT110_LH-L-aP53_R
       175Hmut_7B9_HL-H6 exemplary sequence

<400>  15

Met Gly Thr Ser Leu Leu Cys Trp Met Ala Leu Cys Leu Leu Gly Ala 
1               5                   10                  15      


Asp His Ala Asp Ala Cys Pro Tyr Ser Asn Pro Ser Leu Cys Ser Gly 
            20                  25                  30          


Gly Gly Gly Ser Glu Leu Pro Thr Gln Gly Thr Phe Ser Asn Val Ser 
        35                  40                  45              


Thr Asn Val Ser Pro Ala Lys Pro Thr Thr Thr Ala Cys Pro Tyr Ser 
    50                  55                  60                  


Asn Pro Ser Leu Cys Ser Gly Gly Gly Gly Ser Pro Ala Pro Arg Pro 
65                  70                  75                  80  


Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro 
                85                  90                  95      


Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu 
            100                 105                 110         


Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys 
        115                 120                 125             


Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Asn His Arg 
    130                 135                 140                 


Asn Arg Arg Arg Val Cys Lys Cys Pro Arg Pro Val Val Arg Ala Glu 
145                 150                 155                 160 


Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu Glu Asn Pro Gly 
                165                 170                 175     


Pro Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val 
            180                 185                 190         


Pro Gly Ser Thr Gly Asp Val Leu Met Thr Gln Thr Pro Leu Thr Leu 
        195                 200                 205             


Ser Val Thr Ile Gly Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln 
    210                 215                 220                 


Ser Leu Leu Asp Ser Asp Gly Lys Thr Tyr Leu Asn Trp Leu Leu Gln 
225                 230                 235                 240 


Arg Pro Gly Gln Ser Pro Lys Arg Leu Ile Tyr Leu Val Ser Lys Leu 
                245                 250                 255     


Asp Ser Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp 
            260                 265                 270         


Phe Thr Leu Lys Ile Asn Arg Val Glu Ala Glu Asp Leu Gly Val Tyr 
        275                 280                 285             


Tyr Cys Trp Gln Gly Thr His Ser Pro Leu Thr Phe Gly Ala Gly Thr 
    290                 295                 300                 


Lys Leu Glu Ile Lys Arg Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
305                 310                 315                 320 


Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu 
                325                 330                 335     


Leu Val Arg Ser Gly Ala Ser Val Lys Leu Ser Cys Thr Ala Ser Gly 
            340                 345                 350         


Phe Asn Ile Lys Asp Tyr Tyr Met His Trp Val Lys Gln Arg Pro Glu 
        355                 360                 365             


Gln Gly Leu Glu Trp Ile Gly Trp Ile Asp Pro Glu Asn Gly Asp Thr 
    370                 375                 380                 


Glu Tyr Ala Pro Lys Phe Gln Gly Lys Ala Thr Met Thr Ala Asp Thr 
385                 390                 395                 400 


Ser Ser Asn Thr Ala Tyr Leu Gln Leu Ser Ser Leu Ala Ser Glu Asp 
                405                 410                 415     


Thr Ala Val Tyr Tyr Cys Asn Phe Tyr Gly Asp Ala Leu Asp Tyr Trp 
            420                 425                 430         


Gly Gln Gly Thr Thr Val Thr Val Ser Ser Asp Pro Ala Glu Pro Lys 
        435                 440                 445             


Ser Pro Asp Lys Thr His Thr Cys Pro Pro Cys Pro Lys Asp Pro Lys 
    450                 455                 460                 


Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu 
465                 470                 475                 480 


Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Arg Ser Lys Arg Gly 
                485                 490                 495     


Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val 
            500                 505                 510         


Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu 
        515                 520                 525             


Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp 
    530                 535                 540                 


Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn 
545                 550                 555                 560 


Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg 
                565                 570                 575     


Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly 
            580                 585                 590         


Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu 
        595                 600                 605             


Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu 
    610                 615                 620                 


Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His 
625                 630                 635                 640 


Met Gln Ala Leu Pro Pro Arg Gln Cys Thr Asn Tyr Ala Leu Leu Lys 
                645                 650                 655     


Leu Ala Gly Asp Val Glu Ser Asn Pro Gly Pro Met Tyr Arg Met Gln 
            660                 665                 670         


Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu Val Thr Asn Ser Glu 
        675                 680                 685             


Leu Val Met Thr Gln Ser Pro Ser Ser Leu Thr Val Thr Ala Gly Glu 
    690                 695                 700                 


Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser Gly 
705                 710                 715                 720 


Asn Gln Lys Asn Tyr Leu Thr Trp Tyr Gln Gln Lys Pro Gly Gln Pro 
                725                 730                 735     


Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro 
            740                 745                 750         


Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 
        755                 760                 765             


Ser Ser Val Gln Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Asn Asp 
    770                 775                 780                 


Tyr Ser Tyr Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Ile Lys 
785                 790                 795                 800 


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 
                805                 810                 815     


Val Gln Leu Leu Glu Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Thr 
            820                 825                 830         


Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ala Phe Thr Asn Tyr 
        835                 840                 845             


Trp Leu Gly Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile 
    850                 855                 860                 


Gly Asp Ile Phe Pro Gly Ser Gly Asn Ile His Tyr Asn Glu Lys Phe 
865                 870                 875                 880 


Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr 
                885                 890                 895     


Met Gln Leu Ser Ser Leu Thr Phe Glu Asp Ser Ala Val Tyr Phe Cys 
            900                 905                 910         


Ala Arg Leu Arg Asn Trp Asp Glu Pro Met Asp Tyr Trp Gly Gln Gly 
        915                 920                 925             


Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly Ser Glu Val Gln Leu 
    930                 935                 940                 


Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala Ser Val Lys Ile 
945                 950                 955                 960 


Ser Cys Lys Thr Ser Gly Tyr Thr Phe Thr Glu Tyr Thr Met His Trp 
                965                 970                 975     


Met Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile Gly Arg Ile Asn 
            980                 985                 990         


Pro Tyr Ser Gly Gly Thr Val Tyr  Asn Gln Lys Phe Lys  Gly Lys Ala 
        995                 1000                 1005             


Thr Leu  Thr Val Asp Lys Ser  Ser Ser Thr Ala Tyr  Met Glu Leu 
    1010                 1015                 1020             


Arg Ser  Leu Thr Ser Asp Asp  Ser Ala Val Tyr Tyr  Cys Ala Arg 
    1025                 1030                 1035             


Trp Gly  Gly Asp Tyr Val Thr  Gly Gly Gly Thr Thr  Leu Thr Val 
    1040                 1045                 1050             


Ser Ser  Gly Gly Gly Gly Ser  Gly Gly Gly Gly Ser  Gly Gly Gly 
    1055                 1060                 1065             


Gly Ser  Asp Ile Val Met Thr  Gln Ser Pro Ser Ser  Leu Ser Val 
    1070                 1075                 1080             


Ser Gly  Gly Glu Lys Val Thr  Met Ser Cys Lys Ser  Ser Gln Ser 
    1085                 1090                 1095             


Leu Leu  Asn Ser Gly Asn Gln  Lys Ser Asn Leu Ala  Trp Tyr Gln 
    1100                 1105                 1110             


Gln Lys  Pro Gly Gln Pro Pro  Lys Leu Leu Ile Tyr  Gly Ala Ser 
    1115                 1120                 1125             


Thr Arg  Glu Ser Gly Val Pro  Asp Arg Phe Ala Gly  Ser Gly Ser 
    1130                 1135                 1140             


Gly Thr  Asp Phe Thr Leu Thr  Ile Ser Ser Val Gln  Ala Glu Asp 
    1145                 1150                 1155             


Leu Ala  Val Tyr Tyr Cys Gln  Asn Asp His Ser Tyr  Pro Leu Thr 
    1160                 1165                 1170             


Phe Gly  Gly Gly Thr Lys Leu  Glu Leu Lys Arg Ser  Gly Gly Gly 
    1175                 1180                 1185             


Gly Ser  His His His His His  His 
    1190                 1195     


<210>  16
<211>  1196
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  RQR8-2A-aP53_421_LH-HNG-CD28TM-41BBZ-E2A-aEpCAM_MT110_LH-L-aCD19_
       FMC63_HL-H6 exemplary sequence

<400>  16

Met Gly Thr Ser Leu Leu Cys Trp Met Ala Leu Cys Leu Leu Gly Ala 
1               5                   10                  15      


Asp His Ala Asp Ala Cys Pro Tyr Ser Asn Pro Ser Leu Cys Ser Gly 
            20                  25                  30          


Gly Gly Gly Ser Glu Leu Pro Thr Gln Gly Thr Phe Ser Asn Val Ser 
        35                  40                  45              


Thr Asn Val Ser Pro Ala Lys Pro Thr Thr Thr Ala Cys Pro Tyr Ser 
    50                  55                  60                  


Asn Pro Ser Leu Cys Ser Gly Gly Gly Gly Ser Pro Ala Pro Arg Pro 
65                  70                  75                  80  


Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro 
                85                  90                  95      


Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu 
            100                 105                 110         


Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys 
        115                 120                 125             


Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Asn His Arg 
    130                 135                 140                 


Asn Arg Arg Arg Val Cys Lys Cys Pro Arg Pro Val Val Arg Ala Glu 
145                 150                 155                 160 


Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu Glu Asn Pro Gly 
                165                 170                 175     


Pro Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val 
            180                 185                 190         


Pro Gly Ser Thr Gly Asp Val Leu Met Thr Gln Thr Pro Leu Thr Leu 
        195                 200                 205             


Ser Val Thr Ile Gly Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln 
    210                 215                 220                 


Ser Leu Leu Asp Ser Asp Gly Lys Thr Tyr Leu Asn Trp Leu Leu Gln 
225                 230                 235                 240 


Arg Pro Gly Gln Ser Pro Lys Arg Leu Ile Tyr Leu Val Ser Lys Leu 
                245                 250                 255     


Asp Ser Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp 
            260                 265                 270         


Phe Thr Leu Lys Ile Asn Arg Val Glu Ala Glu Asp Leu Gly Val Tyr 
        275                 280                 285             


Tyr Cys Trp Gln Gly Thr His Ser Pro Leu Thr Phe Gly Ala Gly Thr 
    290                 295                 300                 


Lys Leu Glu Ile Lys Arg Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
305                 310                 315                 320 


Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu 
                325                 330                 335     


Leu Val Arg Ser Gly Ala Ser Val Lys Leu Ser Cys Thr Ala Ser Gly 
            340                 345                 350         


Phe Asn Ile Lys Asp Tyr Tyr Met His Trp Val Lys Gln Arg Pro Glu 
        355                 360                 365             


Gln Gly Leu Glu Trp Ile Gly Trp Ile Asp Pro Glu Asn Gly Asp Thr 
    370                 375                 380                 


Glu Tyr Ala Pro Lys Phe Gln Gly Lys Ala Thr Met Thr Ala Asp Thr 
385                 390                 395                 400 


Ser Ser Asn Thr Ala Tyr Leu Gln Leu Ser Ser Leu Ala Ser Glu Asp 
                405                 410                 415     


Thr Ala Val Tyr Tyr Cys Asn Phe Tyr Gly Asp Ala Leu Asp Tyr Trp 
            420                 425                 430         


Gly Gln Gly Thr Thr Val Thr Val Ser Ser Asp Pro Ala Glu Pro Lys 
        435                 440                 445             


Ser Pro Asp Lys Thr His Thr Cys Pro Pro Cys Pro Lys Asp Pro Lys 
    450                 455                 460                 


Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu 
465                 470                 475                 480 


Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Arg Ser Lys Arg Gly 
                485                 490                 495     


Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val 
            500                 505                 510         


Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu 
        515                 520                 525             


Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp 
    530                 535                 540                 


Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn 
545                 550                 555                 560 


Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg 
                565                 570                 575     


Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly 
            580                 585                 590         


Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu 
        595                 600                 605             


Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu 
    610                 615                 620                 


Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His 
625                 630                 635                 640 


Met Gln Ala Leu Pro Pro Arg Gln Cys Thr Asn Tyr Ala Leu Leu Lys 
                645                 650                 655     


Leu Ala Gly Asp Val Glu Ser Asn Pro Gly Pro Met Tyr Arg Met Gln 
            660                 665                 670         


Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu Val Thr Asn Ser Glu 
        675                 680                 685             


Leu Val Met Thr Gln Ser Pro Ser Ser Leu Thr Val Thr Ala Gly Glu 
    690                 695                 700                 


Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser Gly 
705                 710                 715                 720 


Asn Gln Lys Asn Tyr Leu Thr Trp Tyr Gln Gln Lys Pro Gly Gln Pro 
                725                 730                 735     


Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro 
            740                 745                 750         


Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 
        755                 760                 765             


Ser Ser Val Gln Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Asn Asp 
    770                 775                 780                 


Tyr Ser Tyr Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Ile Lys 
785                 790                 795                 800 


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 
                805                 810                 815     


Val Gln Leu Leu Glu Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Thr 
            820                 825                 830         


Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ala Phe Thr Asn Tyr 
        835                 840                 845             


Trp Leu Gly Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile 
    850                 855                 860                 


Gly Asp Ile Phe Pro Gly Ser Gly Asn Ile His Tyr Asn Glu Lys Phe 
865                 870                 875                 880 


Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr 
                885                 890                 895     


Met Gln Leu Ser Ser Leu Thr Phe Glu Asp Ser Ala Val Tyr Phe Cys 
            900                 905                 910         


Ala Arg Leu Arg Asn Trp Asp Glu Pro Met Asp Tyr Trp Gly Gln Gly 
        915                 920                 925             


Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly Ser Glu Val Lys Leu 
    930                 935                 940                 


Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser Val 
945                 950                 955                 960 


Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp 
                965                 970                 975     


Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile Trp 
            980                 985                 990         


Gly Ser Glu Thr Thr Tyr Tyr Asn  Ser Ala Leu Lys Ser  Arg Leu Thr 
        995                 1000                 1005             


Ile Ile  Lys Asp Asn Ser Lys  Ser Gln Val Phe Leu  Lys Met Asn 
    1010                 1015                 1020             


Ser Leu  Gln Thr Asp Asp Thr  Ala Ile Tyr Tyr Cys  Ala Lys His 
    1025                 1030                 1035             


Tyr Tyr  Tyr Gly Gly Ser Tyr  Ala Met Asp Tyr Trp  Gly Gln Gly 
    1040                 1045                 1050             


Thr Ser  Val Thr Val Ser Ser  Gly Gly Gly Gly Ser  Gly Gly Gly 
    1055                 1060                 1065             


Gly Ser  Gly Gly Gly Gly Ser  Asp Ile Gln Met Thr  Gln Thr Thr 
    1070                 1075                 1080             


Ser Ser  Leu Ser Ala Ser Leu  Gly Asp Arg Val Thr  Ile Ser Cys 
    1085                 1090                 1095             


Arg Ala  Ser Gln Asp Ile Ser  Lys Tyr Leu Asn Trp  Tyr Gln Gln 
    1100                 1105                 1110             


Lys Pro  Asp Gly Thr Val Lys  Leu Leu Ile Tyr His  Thr Ser Arg 
    1115                 1120                 1125             


Leu His  Ser Gly Val Pro Ser  Arg Phe Ser Gly Ser  Gly Ser Gly 
    1130                 1135                 1140             


Thr Asp  Tyr Ser Leu Thr Ile  Ser Asn Leu Glu Gln  Glu Asp Ile 
    1145                 1150                 1155             


Ala Thr  Tyr Phe Cys Gln Gln  Gly Asn Thr Leu Pro  Tyr Thr Phe 
    1160                 1165                 1170             


Gly Gly  Gly Thr Lys Leu Glu  Ile Thr Lys Ala Ser  Gly Gly Gly 
    1175                 1180                 1185             


Gly Ser  His His His His His  His 
    1190                 1195     


<210>  17
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  flexible linker

<400>  17

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10                  15  


<210>  18
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  serine-glycine linker

<400>  18

Gly Gly Gly Gly Ser 
1               5   
