                         SEQUENCE LISTING

<110>  SORRENTO THERAPEUTICS, INC.
 
<120>  CD19-Directed Chimeric Antigen Receptor Constructs

<130>  01223-0087-00PCT

<150>  US 63/090,440
<151>  2020-10-12

<160>  27    

<170>  PatentIn version 3.5

<210>  1
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Anti-CD19 antibody, variable light chain

<400>  1

Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 
            20                  25                  30          


Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile 
        35                  40                  45              


Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln 
65                  70                  75                  80  


Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr 
            100                 105         


<210>  2
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Anti-CD19 antibody,  variable heavy chain

<400>  2

Glu Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln 
1               5                   10                  15      


Ser Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr 
            20                  25                  30          


Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu 
        35                  40                  45              


Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys 
    50                  55                  60                  


Ser Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu 
65                  70                  75                  80  


Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala 
                85                  90                  95      


Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Ser Val Thr Val Ser Ser 
        115                 120 


<210>  3
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker connecting VH and VL- amino acid

<400>  3

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


<210>  4
<211>  46
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD8 hinge region- amino acid

<400>  4

Ala Lys Pro Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro 
1               5                   10                  15      


Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro 
            20                  25                  30          


Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala 
        35                  40                  45      


<210>  5
<211>  40
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD28 extracellular domain/ spacer- amino acid

<400>  5

Lys Ile Glu Val Met Tyr Pro Pro Pro Tyr Leu Asp Asn Glu Lys Ser 
1               5                   10                  15      


Asn Gly Thr Ile Ile His Val Lys Gly Lys His Leu Cys Pro Ser Pro 
            20                  25                  30          


Leu Phe Pro Gly Pro Ser Lys Pro 
        35                  40  


<210>  6
<211>  27
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD28 transmembrane domain- amino acid

<400>  6

Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu 
1               5                   10                  15      


Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val 
            20                  25          


<210>  7
<211>  41
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD28 intracellular signaling domain- amino acid

<400>  7

Arg Ser Lys Arg Ser Arg Leu Leu His Ser Asp Tyr Met Asn Met Thr 
1               5                   10                  15      


Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro 
            20                  25                  30          


Pro Arg Asp Phe Ala Ala Tyr Arg Ser 
        35                  40      


<210>  8
<211>  113
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD3-zeta signaling domain- amino acid

<400>  8

Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly 
1               5                   10                  15      


Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr 
            20                  25                  30          


Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys 
        35                  40                  45              


Pro Gln Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln 
    50                  55                  60                  


Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu 
65                  70                  75                  80  


Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr 
                85                  90                  95      


Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro 
            100                 105                 110         


Arg 
    


<210>  9
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  signal peptide from mouse antibody heavy chain - amino acid

<400>  9

Met Glu Trp Ser Trp Val Phe Leu Phe Phe Leu Ser Val Thr Thr Gly 
1               5                   10                  15      


Val His Ser 
            


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

<220>
<223>  myc tag - amino acid

<400>  10

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


<210>  11
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  myc tag with 2 additional amino acids - amino acid

<400>  11

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


<210>  12
<211>  242
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD19 scFv - amino acid

<400>  12

Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 
            20                  25                  30          


Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile 
        35                  40                  45              


Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln 
65                  70                  75                  80  


Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Gly Gly Gly Gly Ser 
            100                 105                 110         


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Lys Leu Gln Glu 
        115                 120                 125             


Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser Val Thr Cys 
    130                 135                 140                 


Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg 
145                 150                 155                 160 


Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Gly Ser 
                165                 170                 175     


Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu Thr Ile Ile 
            180                 185                 190         


Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn Ser Leu Gln 
        195                 200                 205             


Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly 
    210                 215                 220                 


Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val 
225                 230                 235                 240 


Ser Ser 
        


<210>  13
<211>  88
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Hinge sequence- amino acid

<400>  13

Ala Lys Pro Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro 
1               5                   10                  15      


Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro 
            20                  25                  30          


Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Pro Arg 
        35                  40                  45              


Lys Ile Glu Val Met Tyr Pro Pro Pro Tyr Leu Asp Asn Glu Lys Ser 
    50                  55                  60                  


Asn Gly Thr Ile Ile His Val Lys Gly Lys His Leu Cys Pro Ser Pro 
65                  70                  75                  80  


Leu Phe Pro Gly Pro Ser Lys Pro 
                85              


<210>  14
<211>  541
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD19 CAR2-63 - amino acid

<400>  14

Met Glu Trp Ser Trp Val Phe Leu Phe Phe Leu Ser Val Thr Thr Gly 
1               5                   10                  15      


Val His Ser Asp Ile Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Asp 
            20                  25                  30          


Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly Asp 
        35                  40                  45              


Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu 
    50                  55                  60                  


Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile Tyr 
65                  70                  75                  80  


His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser 
                85                  90                  95      


Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln Glu 
            100                 105                 110         


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


Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr 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 Ala Lys Pro Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala 
        275                 280                 285             


Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg 
    290                 295                 300                 


Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Pro 
305                 310                 315                 320 


Arg Lys Ile Glu Val Met Tyr Pro Pro Pro Tyr Leu Asp Asn Glu Lys 
                325                 330                 335     


Ser Asn Gly Thr Ile Ile His Val Lys Gly Lys His Leu Cys Pro Ser 
            340                 345                 350         


Pro Leu Phe Pro Gly Pro Ser Lys Pro Phe Trp Val Leu Val Val Val 
        355                 360                 365             


Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile 
    370                 375                 380                 


Ile Phe Trp Val Arg Ser Lys Arg Ser Arg Leu Leu His Ser Asp Tyr 
385                 390                 395                 400 


Met Asn Met Thr Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln 
                405                 410                 415     


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


Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln 
        435                 440                 445             


Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu 
    450                 455                 460                 


Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg 
465                 470                 475                 480 


Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met 
                485                 490                 495     


Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly 
            500                 505                 510         


Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp 
        515                 520                 525             


Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
    530                 535                 540     


<210>  15
<211>  1626
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  DNA sequence encoding anti-CD19 CAR2-63

<400>  15
atggagtggt cctgggtgtt cctgtttttc ctgagcgtca caaccggtgt gcatagtgat       60

attgagcaga agctgattag cgaagaggac ctggatatcc agatgacaca gaccaccagc      120

agcctgagcg ccagcctggg cgaccgagtg actatcagct gccgggcatc ccaggatatt      180

tctaagtatc tgaactggta ccagcagaag cccgacggca ctgtcaaact gctgatctac      240

cacaccagta gactgcattc aggggtgcct agcaggttct ccggatctgg cagtgggact      300

gactactccc tgaccatctc taacctggag caggaagata ttgccaccta tttctgccag      360

cagggcaata cactgcctta cacttttggc gggggaacaa agctggagat cactggcgga      420

ggaggatctg gaggaggagg aagtggagga ggaggatcag aggtgaaact gcaggaaagc      480

ggaccaggac tggtcgcacc ttcacagagc ctgtccgtga catgtactgt ctccggagtg      540

tctctgcccg attacggcgt ctcttggatc cggcagcccc ctagaaaggg actggagtgg      600

ctgggcgtga tctggggaag tgaaactacc tactataata gtgctctgaa atcaagactg      660

accatcatta aggacaactc taaaagtcag gtgtttctga agatgaattc cctgcagacc      720

gacgatacag caatctacta ttgcgccaaa cactactatt acggcgggag ctatgccatg      780

gattactggg ggcagggaac ttccgtcacc gtgagcagcg ctaagcccac cacgacgcca      840

gcgccgcgac caccaacacc ggcgcccacc atcgcgtcgc agcccctgtc cctgcgccca      900

gaggcgtgcc ggccagcggc ggggggcgca gtgcacacga gggggctgga cttcgcccct      960

aggaaaattg aagttatgta tcctcctcct tacctagaca atgagaagag caatggaacc     1020

attatccatg tgaaagggaa acacctttgt ccaagtcccc tatttcccgg accttctaag     1080

cccttttggg tgctggtggt ggttggtgga gtcctggctt gctatagctt gctagtaaca     1140

gtggccttta ttattttctg ggtgaggagt aagaggagca ggctcctgca cagtgactac     1200

atgaacatga ctccccgccg ccccgggccc acccgcaagc attaccagcc ctatgcccca     1260

ccacgcgact tcgcagccta tcgctccaga gtgaagttca gcaggagcgc agacgccccc     1320

gcgtaccagc agggccagaa ccagctctat aacgagctca atctaggacg aagagaggag     1380

tacgatgttt tggacaagag acgtggccgg gaccctgaga tggggggaaa gccgagaagg     1440

aagaaccctc aggaaggcct gtacaatgaa ctgcagaaag ataagatggc ggaggcctac     1500

agtgagattg ggatgaaagg cgagcgccgg aggggcaagg ggcacgatgg cctttaccag     1560

ggtctcagta cagccaccaa ggacacctac gacgcccttc acatgcaggc cctgccccct     1620

cgctaa                                                                1626


<210>  16
<211>  8013
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  DNA sequence of the retroviral vector encoding the anti-CD19 
       CAR2-63 (from start codon to stop codon)

<400>  16
aagcttgcat gcctgcaggt cgactctagg cacataaaga aaaacataac taaccaagct       60

gcagccgaga cagtgaaaag aaccgttaaa acggtttgtt ttaaataaac tgaattattt      120

agagtcattt ctttggtagg aaagtacatt ggcacgtaaa ggagcccaaa gcaatctgtg      180

gaaagcccag gctgggagcc cagcagtttg catcccctcc tggcgtgtac ctaagggttt      240

cttaattgtg tggtttctaa atcttccaga gggtttgtct cattcacttc cacttcggtg      300

cacaatactt ggacgcggat ttactgtctt agcatctatc ggtggccctt cgattgaggc      360

tgaacctgag gcccacttct tcagcttgtt aaggagagca caagcaccag aagaggctga      420

cccggcagac ctgtgggcat ttttaacaag ggcctcctgg gtctgtggga ggcaggctta      480

cataaggtgc aaattagaaa tataaataat aagcccatat caatttgtca tcttttttta      540

agctcaagtt ttgaaagacc ccacctgtag gtttggcaag ctagcttaag taacgccatt      600

ttgcaaggca tggaaaatac ataactgaga atagagaagt tcagatcaag gttaggaaca      660

gagagacagc agaatatggg ccaaacagga tatctgtggt aagcagttcc tgccccgctc      720

agggccaaga acagttggaa caggagaata tgggccaaac aggatatctg tggtaagcag      780

ttcctgcccc ggctcagggc caagaacaga tggtccccag atgcggtccc gccctcagca      840

gtttctagag aaccatcaga tgtttccagg gtgccccaag gacctgaaat gaccctgtgc      900

cttatttgaa ctaaccaatc agttcgcttc tcgcttctgt tcgcgcgctt ctgctccccg      960

agctcaataa aagagcccac aacccctcac tcggcgcgcc agtcctccga tagactgcgt     1020

cgcccgggta cccgtattcc caataaagcc tcttgctgtt tgcatccgaa tcgtggactc     1080

gctgatcctt gggagggtct cctcagattg attgactgcc cacctcgggg gtctttcatt     1140

tggaggttcc accgagattt ggagacccct gcccagggac caccgacccc cccgccggga     1200

ggtaagctgg ccagcaactt atctgtgtct gtccgattgt ctagtgtcta tgactgattt     1260

tatgcgcctg cgtcggtact agttagctaa ctagctctgt atctggcgga cccgtggtgg     1320

aactgacgag ttcggaacac ccggccgcaa ccctgggaga cgtcccaggg acttcggggg     1380

ccgtttttgt ggcccgacct gagtcctaaa atcccgatcg tttaggactc tttggtgcac     1440

cccccttaga ggagggatat gtggttctgg taggagacga gaacctaaaa cagttcccgc     1500

ctccgtctga atttttgctt tcggtttggg accgaagccg cgccgcgcgt cttgtctgct     1560

gcagcatcgt tctgtgttgt ctctgtctga ctgtgtttct gtatttgtct gaaaatatgg     1620

gcccgggcta gactgttacc actcccttaa gtttgacctt aggtcactgg aaagatgtcg     1680

agcggatcgc tcacaaccag tcggtagatg tcaagaagag acgttgggtt accttctgct     1740

ctgcagaatg gccaaccttt aacgtcggat ggccgcgaga cggcaccttt aaccgagacc     1800

tcatcaccca ggttaagatc aaggtctttt cacctggccc gcatggacac ccagaccagg     1860

tcccctacat cgtgacctgg gaagccttgg cttttgaccc ccctccctgg gtcaagccct     1920

ttgtacaccc taagcctccg cctcctcttc ctccatccgc cccgtctctc ccccttgaac     1980

ctcctcgttc gaccccgcct cgatcctccc tttatccagc cctcactcct tctctaggcg     2040

cccccatatg gccatatgag atcttatatg gggcaccccc gccccttgta aacttccctg     2100

accctgacat gacaagagtt actaacagcc cctctctcca agctcactta caggctctct     2160

acttagtcca gcacgaagtc tggagacctc tggcggcagc ctaccaagaa caactggacc     2220

gaccggtggt acctcaccct taccgagtcg gcgacacagt gtgggtccgc cgacaccaga     2280

ctaagaacct agaacctcgc tggaaaggac cttacacagt cctgctgacc acccccaccg     2340

ccctcaaagt agacggcatc gcagcttgga tacacgccgc ccacgtgaag gctgccgacc     2400

ccgggggtgg accatcctct agactgcctc gcgaggatcc ctcgaggccg ccaccatgga     2460

gtggtcctgg gtgttcctgt ttttcctgag cgtcacaacc ggtgtgcata gtgatattga     2520

gcagaagctg attagcgaag aggacctgga tatccagatg acacagacca ccagcagcct     2580

gagcgccagc ctgggcgacc gagtgactat cagctgccgg gcatcccagg atatttctaa     2640

gtatctgaac tggtaccagc agaagcccga cggcactgtc aaactgctga tctaccacac     2700

cagtagactg cattcagggg tgcctagcag gttctccgga tctggcagtg ggactgacta     2760

ctccctgacc atctctaacc tggagcagga agatattgcc acctatttct gccagcaggg     2820

caatacactg ccttacactt ttggcggggg aacaaagctg gagatcactg gcggaggagg     2880

atctggagga ggaggaagtg gaggaggagg atcagaggtg aaactgcagg aaagcggacc     2940

aggactggtc gcaccttcac agagcctgtc cgtgacatgt actgtctccg gagtgtctct     3000

gcccgattac ggcgtctctt ggatccggca gccccctaga aagggactgg agtggctggg     3060

cgtgatctgg ggaagtgaaa ctacctacta taatagtgct ctgaaatcaa gactgaccat     3120

cattaaggac aactctaaaa gtcaggtgtt tctgaagatg aattccctgc agaccgacga     3180

tacagcaatc tactattgcg ccaaacacta ctattacggc gggagctatg ccatggatta     3240

ctgggggcag ggaacttccg tcaccgtgag cagcgctaag cccaccacga cgccagcgcc     3300

gcgaccacca acaccggcgc ccaccatcgc gtcgcagccc ctgtccctgc gcccagaggc     3360

gtgccggcca gcggcggggg gcgcagtgca cacgaggggg ctggacttcg cccctaggaa     3420

aattgaagtt atgtatcctc ctccttacct agacaatgag aagagcaatg gaaccattat     3480

ccatgtgaaa gggaaacacc tttgtccaag tcccctattt cccggacctt ctaagccctt     3540

ttgggtgctg gtggtggttg gtggagtcct ggcttgctat agcttgctag taacagtggc     3600

ctttattatt ttctgggtga ggagtaagag gagcaggctc ctgcacagtg actacatgaa     3660

catgactccc cgccgccccg ggcccacccg caagcattac cagccctatg ccccaccacg     3720

cgacttcgca gcctatcgct ccagagtgaa gttcagcagg agcgcagacg cccccgcgta     3780

ccagcagggc cagaaccagc tctataacga gctcaatcta ggacgaagag aggagtacga     3840

tgttttggac aagagacgtg gccgggaccc tgagatgggg ggaaagccga gaaggaagaa     3900

ccctcaggaa ggcctgtaca atgaactgca gaaagataag atggcggagg cctacagtga     3960

gattgggatg aaaggcgagc gccggagggg caaggggcac gatggccttt accagggtct     4020

cagtacagcc accaaggaca cctacgacgc ccttcacatg caggccctgc cccctcgcta     4080

acagccaggg gccgcccaag ggcgaattcg cggccgcatc gatgcatagg ccttccggat     4140

tagtccaatt tgttaaagac aggatatcag tggtccaggc tctagttttg actcaacaat     4200

atcaccagct gaagcctata gagtacgagc catagataaa ataaaagatt ttatttagtc     4260

tccagaaaaa ggggggaatg aaagacccca cctgtaggtt tggcaagcta gcttaagtaa     4320

cgccattttg caaggcatgg aaaatacata actgagaata gagaagttca gatcaaggtt     4380

aggaacagag agacagcaga atatgggcca aacaggatat ctgtggtaag cagttcctgc     4440

cccgctcagg gccaagaaca gttggaacag gagaatatgg gccaaacagg atatctgtgg     4500

taagcagttc ctgccccggc tcagggccaa gaacagatgg tccccagatg cggtcccgcc     4560

ctcagcagtt tctagagaac catcagatgt ttccagggtg ccccaaggac ctgaaatgac     4620

cctgtgcctt atttgaacta accaatcagt tcgcttctcg cttctgttcg cgcgcttctg     4680

ctccccgagc tcaataaaag agcccacaac ccctcactcg gcgcgccagt cctccgatag     4740

actgcgtcgc ccgggtaccc gtgttctcaa taaaccctct tgcagttgca tccgactcgt     4800

ggtctcgctg ttccttggga gggtctcctc tgagtgattg actacccgtc agcggggtct     4860

ttcagtttct cccacctaca caggtctcac taacattcct gatgtgccgc agggactccg     4920

tcagcccggt ttttgtttat aataaaatgc aagaacagtg ttcccttcaa gccagactac     4980

atcctgactc tcggctttat aaaagaatgt tgaagggctc tgtggactat ctgccacacg     5040

actttttaag atttttatgc ctcctggatg agggatttag tcaatctatc ctcgtctatt     5100

ttgctggctt ctccgtattt taaatttcta gtttgcactc ccttcctgag agcacggcga     5160

ttgcagagta gttaatactc tgagggcagg cttctgtgaa aaggttgcct gggctcagtg     5220

tgagattttg ccataaaaag gggtcctgcc cctgtgtaca gacagatcgg aatctagagt     5280

gcatactcag agtccccgcg gttccggggc tctgatctca gggcatcttt gcctagagat     5340

cctctacgcc ggacgcatcg tggccgggta ccgagctcga attcgtaatc atggtcatag     5400

ctgtttcctg tgtgaaattg ttatccgctc acaattccac acaacatacg agccggaagc     5460

ataaagtgta aagcctgggg tgcctaatga gtgagctaac tcacattaat tgcgttgcgc     5520

tcactgcccg ctttccagtc gggaaacctg tcgtgccagc tgcattaatg aatcggccaa     5580

cgcgcgggga gaggcggttt gcgtattggg cgctcttccg cttcctcgct cactgactcg     5640

ctgcgctcgg tcgttcggct gcggcgagcg gtatcagctc actcaaaggc ggtaatacgg     5700

ttatccacag aatcagggga taacgcagga aagaacatgt gagcaaaagg ccagcaaaag     5760

gccaggaacc gtaaaaaggc cgcgttgctg gcgtttttcc ataggctccg cccccctgac     5820

gagcatcaca aaaatcgacg ctcaagtcag aggtggcgaa acccgacagg actataaaga     5880

taccaggcgt ttccccctgg aagctccctc gtgcgctctc ctgttccgac cctgccgctt     5940

accggatacc tgtccgcctt tctcccttcg ggaagcgtgg cgctttctca tagctcacgc     6000

tgtaggtatc tcagttcggt gtaggtcgtt cgctccaagc tgggctgtgt gcacgaaccc     6060

cccgttcagc ccgaccgctg cgccttatcc ggtaactatc gtcttgagtc caacccggta     6120

agacacgact tatcgccact ggcagcagcc actggtaaca ggattagcag agcgaggtat     6180

gtaggcggtg ctacagagtt cttgaagtgg tggcctaact acggctacac tagaaggaca     6240

gtatttggta tctgcgctct gctgaagcca gttaccttcg gaaaaagagt tggtagctct     6300

tgatccggca aacaaaccac cgctggtagc ggtggttttt ttgtttgcaa gcagcagatt     6360

acgcgcagaa aaaaaggatc tcaagaagat cctttgatct tttctacggg gtctgacgct     6420

cagtggaacg aaaactcacg ttaagggatt ttggtcatga gattatcaaa aaggatcttc     6480

acctagatcc ttttaaatta aaaatgaagt tttaaatcaa tctaaagtat atatgagtaa     6540

acttggtctg acagttacca atgcttaatc agtgaggcac ctatctcagc gatctgtcta     6600

tttcgttcat ccatagttgc ctgactcccc gtcgtgtaga taactacgat acgggagggc     6660

ttaccatctg gccccagtgc tgcaatgata ccgcgagacc cacgctcacc ggctccagat     6720

ttatcagcaa taaaccagcc agccggaagg gccgagcgca gaagtggtcc tgcaacttta     6780

tccgcctcca tccagtctat taattgttgc cgggaagcta gagtaagtag ttcgccagtt     6840

aatagtttgc gcaacgttgt tgccattgct acaggcatcg tggtgtcacg ctcgtcgttt     6900

ggtatggctt cattcagctc cggttcccaa cgatcaaggc gagttacatg atcccccatg     6960

ttgtgcaaaa aagcggttag ctccttcggt cctccgatcg ttgtcagaag taagttggcc     7020

gcagtgttat cactcatggt tatggcagca ctgcataatt ctcttactgt catgccatcc     7080

gtaagatgct tttctgtgac tggtgagtac tcaaccaagt cattctgaga atagtgtatg     7140

cggcgaccga gttgctcttg cccggcgtca atacgggata ataccgcgcc acatagcaga     7200

actttaaaag tgctcatcat tggaaaacgt tcttcggggc gaaaactctc aaggatctta     7260

ccgctgttga gatccagttc gatgtaaccc actcgtgcac ccaactgatc ttcagcatct     7320

tttactttca ccagcgtttc tgggtgagca aaaacaggaa ggcaaaatgc cgcaaaaaag     7380

ggaataaggg cgacacggaa atgttgaata ctcatactct tcctttttca atattattga     7440

agcatttatc agggttattg tctcatgagc ggatacatat ttgaatgtat ttagaaaaat     7500

aaacaaatag gggttccgcg cacatttccc cgaaaagtgc cacctgacgt ctaagaaacc     7560

attattatca tgacattaac ctataaaaat aggcgtatca cgaggccctt tcgtctcgcg     7620

cgtttcggtg atgacggtga aaacctctga cacatgcagc tcccggagac ggtcacagct     7680

tgtctgtaag cggatgccgg gagcagacaa gcccgtcagg gcgcgtcagc gggtgttggc     7740

gggtgtcggg gctggcttaa ctatgcggca tcagagcaga ttgtactgag agtgcaccat     7800

atgcggtgtg aaataccgca cagatgcgta aggagaaaat accgcatcag gcgccattcg     7860

ccattcaggc tgcgcaactg ttgggaaggg cgatcggtgc gggcctcttc gctattacgc     7920

cagctggcga aagggggatg tgctgcaagg cgattaagtt gggtaacgcc agggttttcc     7980

cagtcacgac gttgtaaaac gacggccagt gcc                                  8013


<210>  17
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  IgG1 upper hinge sequence

<400>  17

Glu Pro Lys Ser Cys Asp Lys Thr His Thr 
1               5                   10  


<210>  18
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  lower hinge/CH2 sequence

<400>  18

Pro Ala Pro Glu Leu Leu Gly Gly Pro 
1               5                   


<210>  19
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CH2 region

<400>  19

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
1               5                   10          


<210>  20
<211>  23
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Hinge sequence

<400>  20

Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 
1               5                   10                  15      


Pro Glu Leu Leu Gly Gly Pro 
            20              


<210>  21
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Hinge sequence


<220>
<221>  MISC_FEATURE
<222>  (3)..(3)
<223>  Xaa = Pro, Arg, or Ser

<400>  21

Cys Pro Xaa Cys 
1               


<210>  22
<211>  242
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD19 scFv VH-(G4S)3-VL

<400>  22

Glu Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln 
1               5                   10                  15      


Ser Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr 
            20                  25                  30          


Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu 
        35                  40                  45              


Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys 
    50                  55                  60                  


Ser Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu 
65                  70                  75                  80  


Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala 
                85                  90                  95      


Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Ser Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly 
        115                 120                 125             


Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Thr Thr Ser 
    130                 135                 140                 


Ser Leu Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala 
145                 150                 155                 160 


Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp 
                165                 170                 175     


Gly Thr Val Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly 
            180                 185                 190         


Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu 
        195                 200                 205             


Thr Ile Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln 
    210                 215                 220                 


Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu 
225                 230                 235                 240 


Ile Thr 
        


<210>  23
<211>  522
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD19 CAR2-63 (mature polypeptide)

<400>  23

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


Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly Asp Arg Val Thr 
            20                  25                  30          


Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr 
        35                  40                  45              


Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile Tyr His Thr Ser 
    50                  55                  60                  


Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly 
65                  70                  75                  80  


Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln Glu Asp Ile Ala 
                85                  90                  95      


Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gly 
            100                 105                 110         


Gly Thr Lys Leu Glu Ile Thr Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        115                 120                 125             


Ser Gly Gly Gly Gly Ser Glu Val Lys Leu Gln Glu Ser Gly Pro Gly 
    130                 135                 140                 


Leu Val Ala Pro Ser Gln Ser Leu Ser Val Thr Cys Thr Val Ser Gly 
145                 150                 155                 160 


Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Arg 
                165                 170                 175     


Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr 
            180                 185                 190         


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


Lys Ser Gln Val Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp Thr 
    210                 215                 220                 


Ala Ile Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala 
225                 230                 235                 240 


Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Ala Lys 
                245                 250                 255     


Pro Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile 
            260                 265                 270         


Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala 
        275                 280                 285             


Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Pro Arg Lys Ile 
    290                 295                 300                 


Glu Val Met Tyr Pro Pro Pro Tyr Leu Asp Asn Glu Lys Ser Asn Gly 
305                 310                 315                 320 


Thr Ile Ile His Val Lys Gly Lys His Leu Cys Pro Ser Pro Leu Phe 
                325                 330                 335     


Pro Gly Pro Ser Lys Pro Phe Trp Val Leu Val Val Val Gly Gly Val 
            340                 345                 350         


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


Val Arg Ser Lys Arg Ser Arg Leu Leu His Ser Asp Tyr Met Asn Met 
    370                 375                 380                 


Thr Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala 
385                 390                 395                 400 


Pro Pro Arg Asp Phe Ala Ala Tyr Arg Ser Arg Val Lys Phe Ser Arg 
                405                 410                 415     


Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn 
            420                 425                 430         


Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg 
        435                 440                 445             


Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro 
    450                 455                 460                 


Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala 
465                 470                 475                 480 


Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His 
                485                 490                 495     


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


Ala Leu His Met Gln Ala Leu Pro Pro Arg 
        515                 520         


<210>  24
<211>  529
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD19 CAR2-63a (precursor with signal peptide)

<400>  24

Met Glu Trp Ser Trp Val Phe Leu Phe Phe Leu Ser Val Thr Thr Gly 
1               5                   10                  15      


Val His Ser Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala 
            20                  25                  30          


Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile 
        35                  40                  45              


Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys 
    50                  55                  60                  


Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg 
65                  70                  75                  80  


Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn 
                85                  90                  95      


Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr 
            100                 105                 110         


Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Gly Gly 
        115                 120                 125             


Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Lys 
    130                 135                 140                 


Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser 
145                 150                 155                 160 


Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser 
                165                 170                 175     


Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile 
            180                 185                 190         


Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu 
        195                 200                 205             


Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn 
    210                 215                 220                 


Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr 
225                 230                 235                 240 


Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser 
                245                 250                 255     


Val Thr Val Ser Ser Ala Lys Pro Thr Thr Thr Pro Ala Pro Arg Pro 
            260                 265                 270         


Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro 
        275                 280                 285             


Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu 
    290                 295                 300                 


Asp Phe Ala Pro Arg Lys Ile Glu Val Met Tyr Pro Pro Pro Tyr Leu 
305                 310                 315                 320 


Asp Asn Glu Lys Ser Asn Gly Thr Ile Ile His Val Lys Gly Lys His 
                325                 330                 335     


Leu Cys Pro Ser Pro Leu Phe Pro Gly Pro Ser Lys Pro Phe Trp Val 
            340                 345                 350         


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


Val Ala Phe Ile Ile Phe Trp Val Arg Ser Lys Arg Ser Arg Leu Leu 
    370                 375                 380                 


His Ser Asp Tyr Met Asn Met Thr Pro Arg Arg Pro Gly Pro Thr Arg 
385                 390                 395                 400 


Lys His Tyr Gln Pro Tyr Ala Pro Pro Arg Asp Phe Ala Ala Tyr Arg 
                405                 410                 415     


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


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


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


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


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


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


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


Arg 
    


<210>  25
<211>  1590
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  DNA sequence encoding CD19 CAR2-63a

<400>  25
atggaatggt catgggtctt tctctttttt ctcagcgtga ccaccggagt ccactccgat       60

atccagatga cacagaccac cagcagcctg agcgccagcc tgggcgaccg agtgactatc      120

agctgccggg catcccagga tatttctaag tatctgaact ggtaccagca gaagcccgac      180

ggcactgtca aactgctgat ctaccacacc agtagactgc attcaggggt gcctagcagg      240

ttctccggat ctggcagtgg gactgactac tccctgacca tctctaacct ggagcaggaa      300

gatattgcca cctatttctg ccagcagggc aatacactgc cttacacttt tggcggggga      360

acaaagctgg agatcactgg cggaggagga tctggaggag gaggaagtgg aggaggagga      420

tcagaggtga aactgcagga aagcggacca ggactggtcg caccttcaca gagcctgtcc      480

gtgacatgta ctgtctccgg agtgtctctg cccgattacg gcgtctcttg gatccggcag      540

ccccctagaa agggactgga gtggctgggc gtgatctggg gaagtgaaac tacctactat      600

aatagtgctc tgaaatcaag actgaccatc attaaggaca actctaaaag tcaggtgttt      660

ctgaagatga attccctgca gaccgacgat acagcaatct actattgcgc caaacactac      720

tattacggcg ggagctatgc catggattac tgggggcagg gaacttccgt caccgtgagc      780

agcgctaagc ccaccacgac gccagcgccg cgaccaccaa caccggcgcc caccatcgcg      840

tcgcagcccc tgtccctgcg cccagaggcg tgccggccag cggcgggggg cgcagtgcac      900

acgagggggc tggacttcgc ccctaggaaa attgaagtta tgtatcctcc tccttaccta      960

gacaatgaga agagcaatgg aaccattatc catgtgaaag ggaaacacct ttgtccaagt     1020

cccctatttc ccggaccttc taagcccttt tgggtgctgg tggtggttgg tggagtcctg     1080

gcttgctata gcttgctagt aacagtggcc tttattattt tctgggtgag gagtaagagg     1140

agcaggctcc tgcacagtga ctacatgaac atgactcccc gccgccccgg gcccacccgc     1200

aagcattacc agccctatgc cccaccacgc gacttcgcag cctatcgctc cagagtgaag     1260

ttcagcagga gcgcagacgc ccccgcgtac cagcagggcc agaaccagct ctataacgag     1320

ctcaatctag gacgaagaga ggagtacgat gttttggaca agagacgtgg ccgggaccct     1380

gagatggggg gaaagccgag aaggaagaac cctcaggaag gcctgtacaa tgaactgcag     1440

aaagataaga tggcggaggc ctacagtgag attgggatga aaggcgagcg ccggaggggc     1500

aaggggcacg atggccttta ccagggtctc agtacagcca ccaaggacac ctacgacgcc     1560

cttcacatgc aggccctgcc ccctcgctaa                                      1590


<210>  26
<211>  7976
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  DNA sequence of the retroviral vector encoding the CD19 CAR2-63a

<400>  26
aagcttgcat gcctgcaggt cgactctagg cacataaaga aaaacataac taaccaagct       60

gcagccgaga cagtgaaaag aaccgttaaa acggtttgtt ttaaataaac tgaattattt      120

agagtcattt ctttggtagg aaagtacatt ggcacgtaaa ggagcccaaa gcaatctgtg      180

gaaagcccag gctgggagcc cagcagtttg catcccctcc tggcgtgtac ctaagggttt      240

cttaattgtg tggtttctaa atcttccaga gggtttgtct cattcacttc cacttcggtg      300

cacaatactt ggacgcggat ttactgtctt agcatctatc ggtggccctt cgattgaggc      360

tgaacctgag gcccacttct tcagcttgtt aaggagagca caagcaccag aagaggctga      420

cccggcagac ctgtgggcat ttttaacaag ggcctcctgg gtctgtggga ggcaggctta      480

cataaggtgc aaattagaaa tataaataat aagcccatat caatttgtca tcttttttta      540

agctcaagtt ttgaaagacc ccacctgtag gtttggcaag ctagcttaag taacgccatt      600

ttgcaaggca tggaaaatac ataactgaga atagagaagt tcagatcaag gttaggaaca      660

gagagacagc agaatatggg ccaaacagga tatctgtggt aagcagttcc tgccccgctc      720

agggccaaga acagttggaa caggagaata tgggccaaac aggatatctg tggtaagcag      780

ttcctgcccc ggctcagggc caagaacaga tggtccccag atgcggtccc gccctcagca      840

gtttctagag aaccatcaga tgtttccagg gtgccccaag gacctgaaat gaccctgtgc      900

cttatttgaa ctaaccaatc agttcgcttc tcgcttctgt tcgcgcgctt ctgctccccg      960

agctcaataa aagagcccac aacccctcac tcggcgcgcc agtcctccga tagactgcgt     1020

cgcccgggta cccgtattcc caataaagcc tcttgctgtt tgcatccgaa tcgtggactc     1080

gctgatcctt gggagggtct cctcagattg attgactgcc cacctcgggg gtctttcatt     1140

tggaggttcc accgagattt ggagacccct gcccagggac caccgacccc cccgccggga     1200

ggtaagctgg ccagcaactt atctgtgtct gtccgattgt ctagtgtcta tgactgattt     1260

tatgcgcctg cgtcggtact agttagctaa ctagctctgt atctggcgga cccgtggtgg     1320

aactgacgag ttcggaacac ccggccgcaa ccctgggaga cgtcccaggg acttcggggg     1380

ccgtttttgt ggcccgacct gagtcctaaa atcccgatcg tttaggactc tttggtgcac     1440

cccccttaga ggagggatat gtggttctgg taggagacga gaacctaaaa cagttcccgc     1500

ctccgtctga atttttgctt tcggtttggg accgaagccg cgccgcgcgt cttgtctgct     1560

gcagcatcgt tctgtgttgt ctctgtctga ctgtgtttct gtatttgtct gaaaatatgg     1620

gcccgggcta gactgttacc actcccttaa gtttgacctt aggtcactgg aaagatgtcg     1680

agcggatcgc tcacaaccag tcggtagatg tcaagaagag acgttgggtt accttctgct     1740

ctgcagaatg gccaaccttt aacgtcggat ggccgcgaga cggcaccttt aaccgagacc     1800

tcatcaccca ggttaagatc aaggtctttt cacctggccc gcatggacac ccagaccagg     1860

tcccctacat cgtgacctgg gaagccttgg cttttgaccc ccctccctgg gtcaagccct     1920

ttgtacaccc taagcctccg cctcctcttc ctccatccgc cccgtctctc ccccttgaac     1980

ctcctcgttc gaccccgcct cgatcctccc tttatccagc cctcactcct tctctaggcg     2040

cccccatatg gccatatgag atcttatatg gggcaccccc gccccttgta aacttccctg     2100

accctgacat gacaagagtt actaacagcc cctctctcca agctcactta caggctctct     2160

acttagtcca gcacgaagtc tggagacctc tggcggcagc ctaccaagaa caactggacc     2220

gaccggtggt acctcaccct taccgagtcg gcgacacagt gtgggtccgc cgacaccaga     2280

ctaagaacct agaacctcgc tggaaaggac cttacacagt cctgctgacc acccccaccg     2340

ccctcaaagt agacggcatc gcagcttgga tacacgccgc ccacgtgaag gctgccgacc     2400

ccgggggtgg accatcctct agactgcctc gcgaggatcc ctcgaggccg ccaccatgga     2460

atggtcatgg gtctttctct tttttctcag cgtgaccacc ggagtccact ccgatatcca     2520

gatgacacag accaccagca gcctgagcgc cagcctgggc gaccgagtga ctatcagctg     2580

ccgggcatcc caggatattt ctaagtatct gaactggtac cagcagaagc ccgacggcac     2640

tgtcaaactg ctgatctacc acaccagtag actgcattca ggggtgccta gcaggttctc     2700

cggatctggc agtgggactg actactccct gaccatctct aacctggagc aggaagatat     2760

tgccacctat ttctgccagc agggcaatac actgccttac acttttggcg ggggaacaaa     2820

gctggagatc actggcggag gaggatctgg aggaggagga agtggaggag gaggatcaga     2880

ggtgaaactg caggaaagcg gaccaggact ggtcgcacct tcacagagcc tgtccgtgac     2940

atgtactgtc tccggagtgt ctctgcccga ttacggcgtc tcttggatcc ggcagccccc     3000

tagaaaggga ctggagtggc tgggcgtgat ctggggaagt gaaactacct actataatag     3060

tgctctgaaa tcaagactga ccatcattaa ggacaactct aaaagtcagg tgtttctgaa     3120

gatgaattcc ctgcagaccg acgatacagc aatctactat tgcgccaaac actactatta     3180

cggcgggagc tatgccatgg attactgggg gcagggaact tccgtcaccg tgagcagcgc     3240

taagcccacc acgacgccag cgccgcgacc accaacaccg gcgcccacca tcgcgtcgca     3300

gcccctgtcc ctgcgcccag aggcgtgccg gccagcggcg gggggcgcag tgcacacgag     3360

ggggctggac ttcgccccta ggaaaattga agttatgtat cctcctcctt acctagacaa     3420

tgagaagagc aatggaacca ttatccatgt gaaagggaaa cacctttgtc caagtcccct     3480

atttcccgga ccttctaagc ccttttgggt gctggtggtg gttggtggag tcctggcttg     3540

ctatagcttg ctagtaacag tggcctttat tattttctgg gtgaggagta agaggagcag     3600

gctcctgcac agtgactaca tgaacatgac tccccgccgc cccgggccca cccgcaagca     3660

ttaccagccc tatgccccac cacgcgactt cgcagcctat cgctccagag tgaagttcag     3720

caggagcgca gacgcccccg cgtaccagca gggccagaac cagctctata acgagctcaa     3780

tctaggacga agagaggagt acgatgtttt ggacaagaga cgtggccggg accctgagat     3840

ggggggaaag ccgagaagga agaaccctca ggaaggcctg tacaatgaac tgcagaaaga     3900

taagatggcg gaggcctaca gtgagattgg gatgaaaggc gagcgccgga ggggcaaggg     3960

gcacgatggc ctttaccagg gtctcagtac agccaccaag gacacctacg acgcccttca     4020

catgcaggcc ctgccccctc gctaacagcc aggggccgcc caagggcgaa ttcgcggccg     4080

catcgatcat aggccttccg gattagtcca atttgttaaa gacaggatat cagtggtcca     4140

ggctctagtt ttgactcaac aatatcacca gctgaagcct atagagtacg agccatagat     4200

aaaataaaag attttattta gtctccagaa aaagggggga atgaaagacc ccacctgtag     4260

gtttggcaag ctagcttaag taacgccatt ttgcaaggca tggaaaatac ataactgaga     4320

atagagaagt tcagatcaag gttaggaaca gagagacagc agaatatggg ccaaacagga     4380

tatctgtggt aagcagttcc tgccccgctc agggccaaga acagttggaa caggagaata     4440

tgggccaaac aggatatctg tggtaagcag ttcctgcccc ggctcagggc caagaacaga     4500

tggtccccag atgcggtccc gccctcagca gtttctagag aaccatcaga tgtttccagg     4560

gtgccccaag gacctgaaat gaccctgtgc cttatttgaa ctaaccaatc agttcgcttc     4620

tcgcttctgt tcgcgcgctt ctgctccccg agctcaataa aagagcccac aacccctcac     4680

tcggcgcgcc agtcctccga tagactgcgt cgcccgggta cccgtgttct caataaaccc     4740

tcttgcagtt gcatccgact cgtggtctcg ctgttccttg ggagggtctc ctctgagtga     4800

ttgactaccc gtcagcgggg tctttcagtt tctcccacct acacaggtct cactaacatt     4860

cctgatgtgc cgcagggact ccgtcagccc ggtttttgtt tataataaaa tgcaagaaca     4920

gtgttccctt caagccagac tacatcctga ctctcggctt tataaaagaa tgttgaaggg     4980

ctctgtggac tatctgccac acgacttttt aagattttta tgcctcctgg atgagggatt     5040

tagtcaatct atcctcgtct attttgctgg cttctccgta ttttaaattt ctagtttgca     5100

ctcccttcct gagagcacgg cgattgcaga gtagttaata ctctgagggc aggcttctgt     5160

gaaaaggttg cctgggctca gtgtgagatt ttgccataaa aaggggtcct gcccctgtgt     5220

acagacagat cggaatctag agtgcatact cagagtcccc gcggttccgg ggctctgatc     5280

tcagggcatc tttgcctaga gatcctctac gccggacgca tcgtggccgg gtaccgagct     5340

cgaattcgta atcatggtca tagctgtttc ctgtgtgaaa ttgttatccg ctcacaattc     5400

cacacaacat acgagccgga agcataaagt gtaaagcctg gggtgcctaa tgagtgagct     5460

aactcacatt aattgcgttg cgctcactgc ccgctttcca gtcgggaaac ctgtcgtgcc     5520

agctgcatta atgaatcggc caacgcgcgg ggagaggcgg tttgcgtatt gggcgctctt     5580

ccgcttcctc gctcactgac tcgctgcgct cggtcgttcg gctgcggcga gcggtatcag     5640

ctcactcaaa ggcggtaata cggttatcca cagaatcagg ggataacgca ggaaagaaca     5700

tgtgagcaaa aggccagcaa aaggccagga accgtaaaaa ggccgcgttg ctggcgtttt     5760

tccataggct ccgcccccct gacgagcatc acaaaaatcg acgctcaagt cagaggtggc     5820

gaaacccgac aggactataa agataccagg cgtttccccc tggaagctcc ctcgtgcgct     5880

ctcctgttcc gaccctgccg cttaccggat acctgtccgc ctttctccct tcgggaagcg     5940

tggcgctttc tcatagctca cgctgtaggt atctcagttc ggtgtaggtc gttcgctcca     6000

agctgggctg tgtgcacgaa ccccccgttc agcccgaccg ctgcgcctta tccggtaact     6060

atcgtcttga gtccaacccg gtaagacacg acttatcgcc actggcagca gccactggta     6120

acaggattag cagagcgagg tatgtaggcg gtgctacaga gttcttgaag tggtggccta     6180

actacggcta cactagaagg acagtatttg gtatctgcgc tctgctgaag ccagttacct     6240

tcggaaaaag agttggtagc tcttgatccg gcaaacaaac caccgctggt agcggtggtt     6300

tttttgtttg caagcagcag attacgcgca gaaaaaaagg atctcaagaa gatcctttga     6360

tcttttctac ggggtctgac gctcagtgga acgaaaactc acgttaaggg attttggtca     6420

tgagattatc aaaaaggatc ttcacctaga tccttttaaa ttaaaaatga agttttaaat     6480

caatctaaag tatatatgag taaacttggt ctgacagtta ccaatgctta atcagtgagg     6540

cacctatctc agcgatctgt ctatttcgtt catccatagt tgcctgactc cccgtcgtgt     6600

agataactac gatacgggag ggcttaccat ctggccccag tgctgcaatg ataccgcgag     6660

acccacgctc accggctcca gatttatcag caataaacca gccagccgga agggccgagc     6720

gcagaagtgg tcctgcaact ttatccgcct ccatccagtc tattaattgt tgccgggaag     6780

ctagagtaag tagttcgcca gttaatagtt tgcgcaacgt tgttgccatt gctacaggca     6840

tcgtggtgtc acgctcgtcg tttggtatgg cttcattcag ctccggttcc caacgatcaa     6900

ggcgagttac atgatccccc atgttgtgca aaaaagcggt tagctccttc ggtcctccga     6960

tcgttgtcag aagtaagttg gccgcagtgt tatcactcat ggttatggca gcactgcata     7020

attctcttac tgtcatgcca tccgtaagat gcttttctgt gactggtgag tactcaacca     7080

agtcattctg agaatagtgt atgcggcgac cgagttgctc ttgcccggcg tcaatacggg     7140

ataataccgc gccacatagc agaactttaa aagtgctcat cattggaaaa cgttcttcgg     7200

ggcgaaaact ctcaaggatc ttaccgctgt tgagatccag ttcgatgtaa cccactcgtg     7260

cacccaactg atcttcagca tcttttactt tcaccagcgt ttctgggtga gcaaaaacag     7320

gaaggcaaaa tgccgcaaaa aagggaataa gggcgacacg gaaatgttga atactcatac     7380

tcttcctttt tcaatattat tgaagcattt atcagggtta ttgtctcatg agcggataca     7440

tatttgaatg tatttagaaa aataaacaaa taggggttcc gcgcacattt ccccgaaaag     7500

tgccacctga cgtctaagaa accattatta tcatgacatt aacctataaa aataggcgta     7560

tcacgaggcc ctttcgtctc gcgcgtttcg gtgatgacgg tgaaaacctc tgacacatgc     7620

agctcccgga gacggtcaca gcttgtctgt aagcggatgc cgggagcaga caagcccgtc     7680

agggcgcgtc agcgggtgtt ggcgggtgtc ggggctggct taactatgcg gcatcagagc     7740

agattgtact gagagtgcac catatgcggt gtgaaatacc gcacagatgc gtaaggagaa     7800

aataccgcat caggcgccat tcgccattca ggctgcgcaa ctgttgggaa gggcgatcgg     7860

tgcgggcctc ttcgctatta cgccagctgg cgaaaggggg atgtgctgca aggcgattaa     7920

gttgggtaac gccagggttt tcccagtcac gacgttgtaa aacgacggcc agtgcc         7976


<210>  27
<211>  510
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD19 CAR2-63a, mature polypeptide

<400>  27

Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 
            20                  25                  30          


Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile 
        35                  40                  45              


Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln 
65                  70                  75                  80  


Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Gly Gly Gly Gly Ser 
            100                 105                 110         


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Lys Leu Gln Glu 
        115                 120                 125             


Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser Val Thr Cys 
    130                 135                 140                 


Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg 
145                 150                 155                 160 


Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Gly Ser 
                165                 170                 175     


Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu Thr Ile Ile 
            180                 185                 190         


Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn Ser Leu Gln 
        195                 200                 205             


Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly 
    210                 215                 220                 


Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val 
225                 230                 235                 240 


Ser Ser Ala Lys Pro Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro 
                245                 250                 255     


Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys 
            260                 265                 270         


Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala 
        275                 280                 285             


Pro Arg Lys Ile Glu Val Met Tyr Pro Pro Pro Tyr Leu Asp Asn Glu 
    290                 295                 300                 


Lys Ser Asn Gly Thr Ile Ile His Val Lys Gly Lys His Leu Cys Pro 
305                 310                 315                 320 


Ser Pro Leu Phe Pro Gly Pro Ser Lys Pro Phe Trp Val Leu Val Val 
                325                 330                 335     


Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe 
            340                 345                 350         


Ile Ile Phe Trp Val Arg Ser Lys Arg Ser Arg Leu Leu His Ser Asp 
        355                 360                 365             


Tyr Met Asn Met Thr Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr 
    370                 375                 380                 


Gln Pro Tyr Ala Pro Pro Arg Asp Phe Ala Ala Tyr Arg Ser Arg Val 
385                 390                 395                 400 


Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn 
                405                 410                 415     


Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val 
            420                 425                 430         


Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg 
        435                 440                 445             


Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys 
    450                 455                 460                 


Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg 
465                 470                 475                 480 


Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys 
                485                 490                 495     


Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
            500                 505                 510 


