                         SEQUENCE LISTING

<110>  Universiteit Antwerpen
 
<120>  CELL-BASED THERAPEUTICS TARGETING CD70

<130>  UA-016-PCT

<150>  EP20214352.5
<151>  2020-12-15

<160>  35    

<170>  PatentIn version 3.5

<210>  1
<211>  347
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD27-CAR polypeptide

<400>  1

Ala Thr Pro Ala Pro Lys Ser Cys Pro Glu Arg His Tyr Trp Ala Gln 
1               5                   10                  15      


Gly Lys Leu Cys Cys Gln Met Cys Glu Pro Gly Thr Phe Leu Val Lys 
            20                  25                  30          


Asp Cys Asp Gln His Arg Lys Ala Ala Gln Cys Asp Pro Cys Ile Pro 
        35                  40                  45              


Gly Val Ser Phe Ser Pro Asp His His Thr Arg Pro His Cys Glu Ser 
    50                  55                  60                  


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


Ala Asn Ala Glu Cys Ala Cys Arg Asn Gly Trp Gln Cys Arg Asp Lys 
                85                  90                  95      


Glu Cys Thr Glu Cys Asp Pro Leu Pro Asn Pro Ser Leu Thr Ala Arg 
            100                 105                 110         


Ser Ser Gln Ala Leu Ser Pro His Pro Gln Pro Thr His Leu Pro Tyr 
        115                 120                 125             


Val Ser Glu Met Leu Glu Ala Arg Thr Ala Gly His Met Gln Thr Leu 
    130                 135                 140                 


Ala Asp Phe Arg Gln Leu Pro Ala Arg Thr Leu Ser Thr His Trp Pro 
145                 150                 155                 160 


Pro Gln Arg Ser Leu Cys Ser Ser Asp Phe Ile Arg Ile Leu Val Ile 
                165                 170                 175     


Phe Ser Gly Met Phe Leu Val Phe Thr Leu Ala Gly Ala Leu Phe Leu 
            180                 185                 190         


His Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe 
        195                 200                 205             


Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg 
    210                 215                 220                 


Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser 
225                 230                 235                 240 


Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr 
                245                 250                 255     


Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys 
            260                 265                 270         


Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn 
        275                 280                 285             


Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu 
    290                 295                 300                 


Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly 
305                 310                 315                 320 


His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr 
                325                 330                 335     


Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
            340                 345         


<210>  2
<211>  260
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Ala Arg Pro His Pro Trp Trp Leu Cys Val Leu Gly Thr Leu Val 
1               5                   10                  15      


Gly Leu Ser Ala Thr Pro Ala Pro Lys Ser Cys Pro Glu Arg His Tyr 
            20                  25                  30          


Trp Ala Gln Gly Lys Leu Cys Cys Gln Met Cys Glu Pro Gly Thr Phe 
        35                  40                  45              


Leu Val Lys Asp Cys Asp Gln His Arg Lys Ala Ala Gln Cys Asp Pro 
    50                  55                  60                  


Cys Ile Pro Gly Val Ser Phe Ser Pro Asp His His Thr Arg Pro His 
65                  70                  75                  80  


Cys Glu Ser Cys Arg His Cys Asn Ser Gly Leu Leu Val Arg Asn Cys 
                85                  90                  95      


Thr Ile Thr Ala Asn Ala Glu Cys Ala Cys Arg Asn Gly Trp Gln Cys 
            100                 105                 110         


Arg Asp Lys Glu Cys Thr Glu Cys Asp Pro Leu Pro Asn Pro Ser Leu 
        115                 120                 125             


Thr Ala Arg Ser Ser Gln Ala Leu Ser Pro His Pro Gln Pro Thr His 
    130                 135                 140                 


Leu Pro Tyr Val Ser Glu Met Leu Glu Ala Arg Thr Ala Gly His Met 
145                 150                 155                 160 


Gln Thr Leu Ala Asp Phe Arg Gln Leu Pro Ala Arg Thr Leu Ser Thr 
                165                 170                 175     


His Trp Pro Pro Gln Arg Ser Leu Cys Ser Ser Asp Phe Ile Arg Ile 
            180                 185                 190         


Leu Val Ile Phe Ser Gly Met Phe Leu Val Phe Thr Leu Ala Gly Ala 
        195                 200                 205             


Leu Phe Leu His Gln Arg Arg Lys Tyr Arg Ser Asn Lys Gly Glu Ser 
    210                 215                 220                 


Pro Val Glu Pro Ala Glu Pro Cys His Tyr Ser Cys Pro Arg Glu Glu 
225                 230                 235                 240 


Glu Gly Ser Thr Ile Pro Ile Gln Glu Asp Tyr Arg Lys Pro Glu Pro 
                245                 250                 255     


Ala Cys Ser Pro 
            260 


<210>  3
<211>  172
<212>  PRT
<213>  Homo sapiens

<400>  3

Ala Thr Pro Ala Pro Lys Ser Cys Pro Glu Arg His Tyr Trp Ala Gln 
1               5                   10                  15      


Gly Lys Leu Cys Cys Gln Met Cys Glu Pro Gly Thr Phe Leu Val Lys 
            20                  25                  30          


Asp Cys Asp Gln His Arg Lys Ala Ala Gln Cys Asp Pro Cys Ile Pro 
        35                  40                  45              


Gly Val Ser Phe Ser Pro Asp His His Thr Arg Pro His Cys Glu Ser 
    50                  55                  60                  


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


Ala Asn Ala Glu Cys Ala Cys Arg Asn Gly Trp Gln Cys Arg Asp Lys 
                85                  90                  95      


Glu Cys Thr Glu Cys Asp Pro Leu Pro Asn Pro Ser Leu Thr Ala Arg 
            100                 105                 110         


Ser Ser Gln Ala Leu Ser Pro His Pro Gln Pro Thr His Leu Pro Tyr 
        115                 120                 125             


Val Ser Glu Met Leu Glu Ala Arg Thr Ala Gly His Met Gln Thr Leu 
    130                 135                 140                 


Ala Asp Phe Arg Gln Leu Pro Ala Arg Thr Leu Ser Thr His Trp Pro 
145                 150                 155                 160 


Pro Gln Arg Ser Leu Cys Ser Ser Asp Phe Ile Arg 
                165                 170         


<210>  4
<211>  21
<212>  PRT
<213>  Homo sapiens

<400>  4

Ile Leu Val Ile Phe Ser Gly Met Phe Leu Val Phe Thr Leu Ala Gly 
1               5                   10                  15      


Ala Leu Phe Leu His 
            20      


<210>  5
<211>  48
<212>  PRT
<213>  Homo sapiens

<400>  5

Gln Arg Arg Lys Tyr Arg Ser Asn Lys Gly Glu Ser Pro Val Glu Pro 
1               5                   10                  15      


Ala Glu Pro Cys His Tyr Ser Cys Pro Arg Glu Glu Glu Gly Ser Thr 
            20                  25                  30          


Ile Pro Ile Gln Glu Asp Tyr Arg Lys Pro Glu Pro Ala Cys Ser Pro 
        35                  40                  45              


<210>  6
<211>  112
<212>  PRT
<213>  Homo sapiens

<400>  6

Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys 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 Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys 
    50                  55                  60                  


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


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


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


<210>  7
<211>  42
<212>  PRT
<213>  Homo sapiens

<400>  7

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met 
1               5                   10                  15      


Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe 
            20                  25                  30          


Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu 
        35                  40          


<210>  8
<211>  19
<212>  PRT
<213>  Homo sapiens

<400>  8

Met Ala Arg Pro His Pro Trp Trp Leu Cys Val Leu Gly Thr Leu Val 
1               5                   10                  15      


Gly Leu Ser 
            


<210>  9
<211>  366
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD27-CAR polypeptide

<400>  9

Met Ala Arg Pro His Pro Trp Trp Leu Cys Val Leu Gly Thr Leu Val 
1               5                   10                  15      


Gly Leu Ser Ala Thr Pro Ala Pro Lys Ser Cys Pro Glu Arg His Tyr 
            20                  25                  30          


Trp Ala Gln Gly Lys Leu Cys Cys Gln Met Cys Glu Pro Gly Thr Phe 
        35                  40                  45              


Leu Val Lys Asp Cys Asp Gln His Arg Lys Ala Ala Gln Cys Asp Pro 
    50                  55                  60                  


Cys Ile Pro Gly Val Ser Phe Ser Pro Asp His His Thr Arg Pro His 
65                  70                  75                  80  


Cys Glu Ser Cys Arg His Cys Asn Ser Gly Leu Leu Val Arg Asn Cys 
                85                  90                  95      


Thr Ile Thr Ala Asn Ala Glu Cys Ala Cys Arg Asn Gly Trp Gln Cys 
            100                 105                 110         


Arg Asp Lys Glu Cys Thr Glu Cys Asp Pro Leu Pro Asn Pro Ser Leu 
        115                 120                 125             


Thr Ala Arg Ser Ser Gln Ala Leu Ser Pro His Pro Gln Pro Thr His 
    130                 135                 140                 


Leu Pro Tyr Val Ser Glu Met Leu Glu Ala Arg Thr Ala Gly His Met 
145                 150                 155                 160 


Gln Thr Leu Ala Asp Phe Arg Gln Leu Pro Ala Arg Thr Leu Ser Thr 
                165                 170                 175     


His Trp Pro Pro Gln Arg Ser Leu Cys Ser Ser Asp Phe Ile Arg Ile 
            180                 185                 190         


Leu Val Ile Phe Ser Gly Met Phe Leu Val Phe Thr Leu Ala Gly Ala 
        195                 200                 205             


Leu Phe Leu His Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys 
    210                 215                 220                 


Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys 
225                 230                 235                 240 


Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val 
                245                 250                 255     


Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn 
            260                 265                 270         


Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val 
        275                 280                 285             


Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg 
    290                 295                 300                 


Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys 
305                 310                 315                 320 


Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg 
                325                 330                 335     


Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys 
            340                 345                 350         


Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
        355                 360                 365     


<210>  10
<211>  193
<212>  PRT
<213>  Homo sapiens

<400>  10

Ala Thr Pro Ala Pro Lys Ser Cys Pro Glu Arg His Tyr Trp Ala Gln 
1               5                   10                  15      


Gly Lys Leu Cys Cys Gln Met Cys Glu Pro Gly Thr Phe Leu Val Lys 
            20                  25                  30          


Asp Cys Asp Gln His Arg Lys Ala Ala Gln Cys Asp Pro Cys Ile Pro 
        35                  40                  45              


Gly Val Ser Phe Ser Pro Asp His His Thr Arg Pro His Cys Glu Ser 
    50                  55                  60                  


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


Ala Asn Ala Glu Cys Ala Cys Arg Asn Gly Trp Gln Cys Arg Asp Lys 
                85                  90                  95      


Glu Cys Thr Glu Cys Asp Pro Leu Pro Asn Pro Ser Leu Thr Ala Arg 
            100                 105                 110         


Ser Ser Gln Ala Leu Ser Pro His Pro Gln Pro Thr His Leu Pro Tyr 
        115                 120                 125             


Val Ser Glu Met Leu Glu Ala Arg Thr Ala Gly His Met Gln Thr Leu 
    130                 135                 140                 


Ala Asp Phe Arg Gln Leu Pro Ala Arg Thr Leu Ser Thr His Trp Pro 
145                 150                 155                 160 


Pro Gln Arg Ser Leu Cys Ser Ser Asp Phe Ile Arg Ile Leu Val Ile 
                165                 170                 175     


Phe Ser Gly Met Phe Leu Val Phe Thr Leu Ala Gly Ala Leu Phe Leu 
            180                 185                 190         


His 
    


<210>  11
<211>  579
<212>  DNA
<213>  Homo sapiens

<400>  11
gctacaccag ctcctaagag ctgccccgag agacactatt gggcccaggg caagctgtgc       60

tgccagatgt gtgaacctgg caccttcctg gtcaaggact gcgaccagca cagaaaggcc      120

gctcagtgcg atccttgtat ccccggcgtg tccttctctc ccgaccacca cacaagacct      180

cactgcgaga gctgcagaca ctgcaattct ggactgctcg tgcggaactg caccatcaca      240

gccaatgccg agtgcgcctg cagaaatggc tggcagtgcc gggacaaaga atgtaccgag      300

tgcgaccctc tgcctaatcc tagcctgacc gccagaagca gccaggcttt gtctcctcat      360

cctcagccta cacatctgcc ctacgtgtcc gagatgctgg aagccagaac agccggccat      420

atgcagaccc tggccgactt tagacagctg cccgccagaa cactgagcac ccattggcct      480

ccacagagaa gcctgtgcag cagcgacttc atccggatcc tcgtgatctt cagcggcatg      540

ttcctggtgt tcacactggc tggcgccctg tttctgcat                             579


<210>  12
<211>  336
<212>  DNA
<213>  Homo sapiens

<400>  12
cgcgtgaaat tcagccgcag cgcagatgct ccagcctaca agcaggggca gaaccagctc       60

tacaacgaac tcaatcttgg tcggagagag gagtacgacg tgctggacaa gcggagagga      120

cgggacccag aaatgggcgg gaagccgcgc agaaagaatc cccaagaggg cctgtacaac      180

gagctccaaa aggataagat ggcagaagcc tatagcgaga ttggtatgaa aggggaacgc      240

agaagaggca aaggccacga cggactgtac cagggactca gcaccgccac caaggacacc      300

tatgacgctc ttcacatgca ggccctgccg cctcgg                                336


<210>  13
<211>  126
<212>  DNA
<213>  Homo sapiens

<400>  13
aagcgcggtc ggaagaagct gctgtacatc tttaagcaac ccttcatgag gcctgtgcag       60

actactcaag aggaggacgg ctgttcatgc cggttcccag aggaggagga aggcggctgc      120

gaactg                                                                 126


<210>  14
<211>  1098
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CD27-CAR construct

<400>  14
atggccagac ctcatccttg gtggctgtgt gtgctgggca cactcgttgg cctgtctgct       60

acaccagctc ctaagagctg ccccgagaga cactattggg cccagggcaa gctgtgctgc      120

cagatgtgtg aacctggcac cttcctggtc aaggactgcg accagcacag aaaggccgct      180

cagtgcgatc cttgtatccc cggcgtgtcc ttctctcccg accaccacac aagacctcac      240

tgcgagagct gcagacactg caattctgga ctgctcgtgc ggaactgcac catcacagcc      300

aatgccgagt gcgcctgcag aaatggctgg cagtgccggg acaaagaatg taccgagtgc      360

gaccctctgc ctaatcctag cctgaccgcc agaagcagcc aggctttgtc tcctcatcct      420

cagcctacac atctgcccta cgtgtccgag atgctggaag ccagaacagc cggccatatg      480

cagaccctgg ccgactttag acagctgccc gccagaacac tgagcaccca ttggcctcca      540

cagagaagcc tgtgcagcag cgacttcatc cggatcctcg tgatcttcag cggcatgttc      600

ctggtgttca cactggctgg cgccctgttt ctgcataagc gcggtcggaa gaagctgctg      660

tacatcttta agcaaccctt catgaggcct gtgcagacta ctcaagagga ggacggctgt      720

tcatgccggt tcccagagga ggaggaaggc ggctgcgaac tgcgcgtgaa attcagccgc      780

agcgcagatg ctccagccta caagcagggg cagaaccagc tctacaacga actcaatctt      840

ggtcggagag aggagtacga cgtgctggac aagcggagag gacgggaccc agaaatgggc      900

gggaagccgc gcagaaagaa tccccaagag ggcctgtaca acgagctcca aaaggataag      960

atggcagaag cctatagcga gattggtatg aaaggggaac gcagaagagg caaaggccac     1020

gacggactgt accagggact cagcaccgcc accaaggaca cctatgacgc tcttcacatg     1080

caggccctgc cgcctcgg                                                   1098


<210>  15
<211>  162
<212>  PRT
<213>  Homo sapiens

<400>  15

Met Arg Ile Ser Lys Pro His Leu Arg Ser Ile Ser Ile Gln Cys Tyr 
1               5                   10                  15      


Leu Cys Leu Leu Leu Asn Ser His Phe Leu Thr Glu Ala Gly Ile His 
            20                  25                  30          


Val Phe Ile Leu Gly Cys Phe Ser Ala Gly Leu Pro Lys Thr Glu Ala 
        35                  40                  45              


Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
    50                  55                  60                  


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
65                  70                  75                  80  


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
                85                  90                  95      


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
            100                 105                 110         


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
        115                 120                 125             


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
    130                 135                 140                 


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 
145                 150                 155                 160 


Thr Ser 
        


<210>  16
<211>  486
<212>  DNA
<213>  Homo sapiens

<400>  16
atgagaatca gcaagcccca cctgagatcc atcagcatcc agtgctacct gtgcctgctg       60

ctgaacagcc actttctgac agaggccggc atccacgtgt tcatcctggg ctgtttttct      120

gccggcctgc ctaagaccga ggccaactgg gttaacgtga tcagcgacct gaagaagatc      180

gaggacctga tccagagcat gcacatcgac gccacactgt acaccgagag cgacgtgcac      240

cctagctgta aagtgaccgc catgaagtgc tttctgctgg aactgcaagt gatcagcctg      300

gaaagcggcg acgccagcat ccacgacacc gtggaaaacc tgatcatcct ggccaacaac      360

agcctgagca gcaacggcaa tgtgaccgag tccggctgca aagagtgcga ggaactggaa      420

gagaagaata tcaaagagtt cctgcagagc ttcgtgcaca tcgtgcagat gttcatcaac      480

accagc                                                                 486


<210>  17
<211>  18
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  T2A peptide

<400>  17

Glu Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu Glu Asn Pro 
1               5                   10                  15      


Gly Pro 
        


<210>  18
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  P2A peptide

<400>  18

Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn 
1               5                   10                  15      


Pro Gly Pro 
            


<210>  19
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  E2A peptide

<400>  19

Gln Cys Thr Asn Tyr Ala Leu Leu Lys Leu Ala Gly Asp Val Glu Ser 
1               5                   10                  15      


Asn Pro Gly Pro 
            20  


<210>  20
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  F2A peptide

<400>  20

Val Lys Gln Thr Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val 
1               5                   10                  15      


Glu Ser Asn Pro Gly Pro 
            20          


<210>  21
<211>  554
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CAR-P2A-IL15 polypeptide

<400>  21

Met Ala Arg Pro His Pro Trp Trp Leu Cys Val Leu Gly Thr Leu Val 
1               5                   10                  15      


Gly Leu Ser Ala Thr Pro Ala Pro Lys Ser Cys Pro Glu Arg His Tyr 
            20                  25                  30          


Trp Ala Gln Gly Lys Leu Cys Cys Gln Met Cys Glu Pro Gly Thr Phe 
        35                  40                  45              


Leu Val Lys Asp Cys Asp Gln His Arg Lys Ala Ala Gln Cys Asp Pro 
    50                  55                  60                  


Cys Ile Pro Gly Val Ser Phe Ser Pro Asp His His Thr Arg Pro His 
65                  70                  75                  80  


Cys Glu Ser Cys Arg His Cys Asn Ser Gly Leu Leu Val Arg Asn Cys 
                85                  90                  95      


Thr Ile Thr Ala Asn Ala Glu Cys Ala Cys Arg Asn Gly Trp Gln Cys 
            100                 105                 110         


Arg Asp Lys Glu Cys Thr Glu Cys Asp Pro Leu Pro Asn Pro Ser Leu 
        115                 120                 125             


Thr Ala Arg Ser Ser Gln Ala Leu Ser Pro His Pro Gln Pro Thr His 
    130                 135                 140                 


Leu Pro Tyr Val Ser Glu Met Leu Glu Ala Arg Thr Ala Gly His Met 
145                 150                 155                 160 


Gln Thr Leu Ala Asp Phe Arg Gln Leu Pro Ala Arg Thr Leu Ser Thr 
                165                 170                 175     


His Trp Pro Pro Gln Arg Ser Leu Cys Ser Ser Asp Phe Ile Arg Ile 
            180                 185                 190         


Leu Val Ile Phe Ser Gly Met Phe Leu Val Phe Thr Leu Ala Gly Ala 
        195                 200                 205             


Leu Phe Leu His Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys 
    210                 215                 220                 


Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys 
225                 230                 235                 240 


Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val 
                245                 250                 255     


Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn 
            260                 265                 270         


Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val 
        275                 280                 285             


Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg 
    290                 295                 300                 


Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys 
305                 310                 315                 320 


Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg 
                325                 330                 335     


Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys 
            340                 345                 350         


Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg Glu Phe 
        355                 360                 365             


Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val 
    370                 375                 380                 


Glu Glu Asn Pro Gly Pro Met Arg Ile Ser Lys Pro His Leu Arg Ser 
385                 390                 395                 400 


Ile Ser Ile Gln Cys Tyr Leu Cys Leu Leu Leu Asn Ser His Phe Leu 
                405                 410                 415     


Thr Glu Ala Gly Ile His Val Phe Ile Leu Gly Cys Phe Ser Ala Gly 
            420                 425                 430         


Leu Pro Lys Thr Glu Ala Asn Trp Val Asn Val Ile Ser Asp Leu Lys 
        435                 440                 445             


Lys Ile Glu Asp Leu Ile Gln Ser Met His Ile Asp Ala Thr Leu Tyr 
    450                 455                 460                 


Thr Glu Ser Asp Val His Pro Ser Cys Lys Val Thr Ala Met Lys Cys 
465                 470                 475                 480 


Phe Leu Leu Glu Leu Gln Val Ile Ser Leu Glu Ser Gly Asp Ala Ser 
                485                 490                 495     


Ile His Asp Thr Val Glu Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu 
            500                 505                 510         


Ser Ser Asn Gly Asn Val Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu 
        515                 520                 525             


Leu Glu Glu Lys Asn Ile Lys Glu Phe Leu Gln Ser Phe Val His Ile 
    530                 535                 540                 


Val Gln Met Phe Ile Asn Thr Ser Glu Phe 
545                 550                 


<210>  22
<211>  1683
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CAR-P2A-IL15 construct

<400>  22
actagtgcca ccatggccag acctcatcct tggtggctgt gtgtgctggg cacactcgtt       60

ggcctgtctg ctacaccagc tcctaagagc tgccccgaga gacactattg ggcccagggc      120

aagctgtgct gccagatgtg tgaacctggc accttcctgg tcaaggactg cgaccagcac      180

agaaaggccg ctcagtgcga tccttgtatc cccggcgtgt ccttctctcc cgaccaccac      240

acaagacctc actgcgagag ctgcagacac tgcaattctg gactgctcgt gcggaactgc      300

accatcacag ccaatgccga gtgcgcctgc agaaatggct ggcagtgccg ggacaaagaa      360

tgtaccgagt gcgaccctct gcctaatcct agcctgaccg ccagaagcag ccaggctttg      420

tctcctcatc ctcagcctac acatctgccc tacgtgtccg agatgctgga agccagaaca      480

gccggccata tgcagaccct ggccgacttt agacagctgc ccgccagaac actgagcacc      540

cattggcctc cacagagaag cctgtgcagc agcgacttca tccggatcct cgtgatcttc      600

agcggcatgt tcctggtgtt cacactggct ggcgccctgt ttctgcataa gcgcggtcgg      660

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag      720

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg      780

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac      840

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac      900

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc      960

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga     1020

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac     1080

gctcttcaca tgcaggccct gccgcctcgg gaattcggtt ccggagccac gaacttctct     1140

ctgttaaagc aagcaggaga cgtggaagaa aaccccggtc ccatgagaat cagcaagccc     1200

cacctgagat ccatcagcat ccagtgctac ctgtgcctgc tgctgaacag ccactttctg     1260

acagaggccg gcatccacgt gttcatcctg ggctgttttt ctgccggcct gcctaagacc     1320

gaggccaact gggttaacgt gatcagcgac ctgaagaaga tcgaggacct gatccagagc     1380

atgcacatcg acgccacact gtacaccgag agcgacgtgc accctagctg taaagtgacc     1440

gccatgaagt gctttctgct ggaactgcaa gtgatcagcc tggaaagcgg cgacgccagc     1500

atccacgaca ccgtggaaaa cctgatcatc ctggccaaca acagcctgag cagcaacggc     1560

aatgtgaccg agtccggctg caaagagtgc gaggaactgg aagagaagaa tatcaaagag     1620

ttcctgcaga gcttcgtgca catcgtgcag atgttcatca acaccagcga attctaactc     1680

gag                                                                   1683


<210>  23
<211>  162
<212>  PRT
<213>  Homo sapiens

<400>  23

Met Arg Ser Ser Pro Gly Asn Met Glu Arg Ile Val Ile Cys Leu Met 
1               5                   10                  15      


Val Ile Phe Leu Gly Thr Leu Val His Lys Ser Ser Ser Gln Gly Gln 
            20                  25                  30          


Asp Arg His Met Ile Arg Met Arg Gln Leu Ile Asp Ile Val Asp Gln 
        35                  40                  45              


Leu Lys Asn Tyr Val Asn Asp Leu Val Pro Glu Phe Leu Pro Ala Pro 
    50                  55                  60                  


Glu Asp Val Glu Thr Asn Cys Glu Trp Ser Ala Phe Ser Cys Phe Gln 
65                  70                  75                  80  


Lys Ala Gln Leu Lys Ser Ala Asn Thr Gly Asn Asn Glu Arg Ile Ile 
                85                  90                  95      


Asn Val Ser Ile Lys Lys Leu Lys Arg Lys Pro Pro Ser Thr Asn Ala 
            100                 105                 110         


Gly Arg Arg Gln Lys His Arg Leu Thr Cys Pro Ser Cys Asp Ser Tyr 
        115                 120                 125             


Glu Lys Lys Pro Pro Lys Glu Phe Leu Glu Arg Phe Lys Ser Leu Leu 
    130                 135                 140                 


Gln Lys Met Ile His Gln His Leu Ser Ser Arg Thr His Gly Ser Glu 
145                 150                 155                 160 


Asp Ser 
        


<210>  24
<211>  153
<212>  PRT
<213>  Homo sapiens

<400>  24

Met Arg Ser Ser Pro Gly Asn Met Glu Arg Ile Val Ile Cys Leu Met 
1               5                   10                  15      


Val Ile Phe Leu Gly Thr Leu Val His Lys Ser Ser Ser Gln Gly Gln 
            20                  25                  30          


Asp Arg His Met Ile Arg Met Arg Gln Leu Ile Asp Ile Val Asp Gln 
        35                  40                  45              


Leu Lys Asn Tyr Val Asn Asp Leu Val Pro Glu Phe Leu Pro Ala Pro 
    50                  55                  60                  


Glu Asp Val Glu Thr Asn Cys Glu Trp Ser Ala Phe Ser Cys Phe Gln 
65                  70                  75                  80  


Lys Ala Gln Leu Lys Ser Ala Asn Thr Gly Asn Asn Glu Arg Ile Ile 
                85                  90                  95      


Asn Val Ser Ile Lys Lys Leu Lys Arg Lys Pro Pro Ser Thr Asn Ala 
            100                 105                 110         


Gly Arg Arg Gln Lys His Arg Leu Thr Cys Pro Ser Cys Asp Ser Tyr 
        115                 120                 125             


Glu Lys Lys Pro Pro Lys Glu Phe Leu Glu Arg Phe Lys Ser Leu Leu 
    130                 135                 140                 


Gln Lys Val Ser Thr Leu Ser Phe Ile 
145                 150             


<210>  25
<211>  486
<212>  DNA
<213>  Homo sapiens

<400>  25
atgagatcca gtcctggcaa catggagagg attgtcatct gtctgatggt catcttcttg       60

gggacactgg tccacaaatc aagctcccaa ggtcaagatc gccacatgat tagaatgcgt      120

caacttatag atattgttga tcagctgaaa aattatgtga atgacttggt ccctgaattt      180

ctgccagctc cagaagatgt agagacaaac tgtgagtggt cagctttttc ctgctttcag      240

aaggcccaac taaagtcagc aaatacagga aacaatgaaa ggataatcaa tgtatcaatt      300

aaaaagctga agaggaaacc accttccaca aatgcaggga gaagacagaa acacagacta      360

acatgccctt catgtgattc ttatgagaaa aaaccaccca aagaattcct agaaagattc      420

aaatcacttc tccaaaagat gattcatcag catctgtcct ctagaacaca cggaagtgaa      480

gattcc                                                                 486


<210>  26
<211>  253
<212>  PRT
<213>  Homo sapiens

<400>  26

Met Trp Pro Pro Gly Ser Ala Ser Gln Pro Pro Pro Ser Pro Ala Ala 
1               5                   10                  15      


Ala Thr Gly Leu His Pro Ala Ala Arg Pro Val Ser Leu Gln Cys Arg 
            20                  25                  30          


Leu Ser Met Cys Pro Ala Arg Ser Leu Leu Leu Val Ala Thr Leu Val 
        35                  40                  45              


Leu Leu Asp His Leu Ser Leu Ala Arg Asn Leu Pro Val Ala Thr Pro 
    50                  55                  60                  


Asp Pro Gly Met Phe Pro Cys Leu His His Ser Gln Asn Leu Leu Arg 
65                  70                  75                  80  


Ala Val Ser Asn Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr 
                85                  90                  95      


Pro Cys Thr Ser Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys 
            100                 105                 110         


Thr Ser Thr Val Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu 
        115                 120                 125             


Ser Cys Leu Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys 
    130                 135                 140                 


Leu Ala Ser Arg Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser 
145                 150                 155                 160 


Ile Tyr Glu Asp Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn 
                165                 170                 175     


Ala Lys Leu Leu Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn 
            180                 185                 190         


Met Leu Ala Val Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser 
        195                 200                 205             


Glu Thr Val Pro Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys 
    210                 215                 220                 


Thr Lys Ile Lys Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala 
225                 230                 235                 240 


Val Thr Ile Asp Arg Val Met Ser Tyr Leu Asn Ala Ser 
                245                 250             


<210>  27
<211>  219
<212>  PRT
<213>  Homo sapiens

<400>  27

Met Cys Pro Ala Arg Ser Leu Leu Leu Val Ala Thr Leu Val Leu Leu 
1               5                   10                  15      


Asp His Leu Ser Leu Ala Arg Asn Leu Pro Val Ala Thr Pro Asp Pro 
            20                  25                  30          


Gly Met Phe Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val 
        35                  40                  45              


Ser Asn Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys 
    50                  55                  60                  


Thr Ser Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser 
65                  70                  75                  80  


Thr Val Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys 
                85                  90                  95      


Leu Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala 
            100                 105                 110         


Ser Arg Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr 
        115                 120                 125             


Glu Asp Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys 
    130                 135                 140                 


Leu Leu Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu 
145                 150                 155                 160 


Ala Val Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr 
                165                 170                 175     


Val Pro Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys 
            180                 185                 190         


Ile Lys Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr 
        195                 200                 205             


Ile Asp Arg Val Met Ser Tyr Leu Asn Ala Ser 
    210                 215                 


<210>  28
<211>  328
<212>  PRT
<213>  Homo sapiens

<400>  28

Met Cys His Gln Gln Leu Val Ile Ser Trp Phe Ser Leu Val Phe Leu 
1               5                   10                  15      


Ala Ser Pro Leu Val Ala Ile Trp Glu Leu Lys Lys Asp Val Tyr Val 
            20                  25                  30          


Val Glu Leu Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu 
        35                  40                  45              


Thr Cys Asp Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln 
    50                  55                  60                  


Ser Ser Glu Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys 
65                  70                  75                  80  


Glu Phe Gly Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val 
                85                  90                  95      


Leu Ser His Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp 
            100                 105                 110         


Ser Thr Asp Ile Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe 
        115                 120                 125             


Leu Arg Cys Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp 
    130                 135                 140                 


Leu Thr Thr Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg 
145                 150                 155                 160 


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


Ala Glu Arg Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu 
            180                 185                 190         


Cys Gln Glu Asp Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile 
        195                 200                 205             


Glu Val Met Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr 
    210                 215                 220                 


Ser Ser Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn 
225                 230                 235                 240 


Leu Gln Leu Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp 
                245                 250                 255     


Glu Tyr Pro Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr 
            260                 265                 270         


Phe Cys Val Gln Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg 
        275                 280                 285             


Val Phe Thr Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala 
    290                 295                 300                 


Ser Ile Ser Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser 
305                 310                 315                 320 


Glu Trp Ala Ser Val Pro Cys Ser 
                325             


<210>  29
<211>  657
<212>  DNA
<213>  Homo sapiens

<400>  29
atgtgtccag cgcgcagcct cctccttgtg gctaccctgg tcctcctgga ccacctcagt       60

ttggccagaa acctccccgt ggccactcca gacccaggaa tgttcccatg ccttcaccac      120

tcccaaaacc tgctgagggc cgtcagcaac atgctccaga aggccagaca aactctagaa      180

ttttaccctt gcacttctga agagattgat catgaagata tcacaaaaga taaaaccagc      240

acagtggagg cctgtttacc attggaatta accaagaatg agagttgcct aaattccaga      300

gagacctctt tcataactaa tgggagttgc ctggcctcca gaaagacctc ttttatgatg      360

gccctgtgcc ttagtagtat ttatgaagac ttgaagatgt accaggtgga gttcaagacc      420

atgaatgcaa agcttctgat ggatcctaag aggcagatct ttctagatca aaacatgctg      480

gcagttattg atgagctgat gcaggccctg aatttcaaca gtgagactgt gccacaaaaa      540

tcctcccttg aagaaccgga tttttataaa actaaaatca agctctgcat acttcttcat      600

gctttcagaa ttcgggcagt gactattgat agagtgatga gctatctgaa tgcttcc         657


<210>  30
<211>  984
<212>  DNA
<213>  Homo sapiens

<400>  30
atgtgtcacc agcagttggt catctcttgg ttttccctgg tttttctggc atctcccctc       60

gtggccatat gggaactgaa gaaagatgtt tatgtcgtag aattggattg gtatccggat      120

gcccctggag aaatggtggt cctcacctgt gacacccctg aagaagatgg tatcacctgg      180

accttggacc agagcagtga ggtcttaggc tctggcaaaa ccctgaccat ccaagtcaaa      240

gagtttggag atgctggcca gtacacctgt cacaaaggag gcgaggttct aagccattcg      300

ctcctgctgc ttcacaaaaa ggaagatgga atttggtcca ctgatatttt aaaggaccag      360

aaagaaccca aaaataagac ctttctaaga tgcgaggcca agaattattc tggacgtttc      420

acctgctggt ggctgacgac aatcagtact gatttgacat tcagtgtcaa aagcagcaga      480

ggctcttctg acccccaagg ggtgacgtgc ggagctgcta cactctctgc agagagagtc      540

agaggggaca acaaggagta tgagtactca gtggagtgcc aggaggacag tgcctgccca      600

gctgctgagg agagtctgcc cattgaggtc atggtggatg ccgttcacaa gctcaagtat      660

gaaaactaca ccagcagctt cttcatcagg gacatcatca aacctgaccc acccaagaac      720

ttgcagctga agccattaaa gaattctcgg caggtggagg tcagctggga gtaccctgac      780

acctggagta ctccacattc ctacttctcc ctgacattct gcgttcaggt ccagggcaag      840

agcaagagag aaaagaaaga tagagtcttc acggacaaga cctcagccac ggtcatctgc      900

cgcaaaaatg ccagcattag cgtgcgggcc caggaccgct actatagctc atcttggagc      960

gaatgggcat ctgtgccctg cagt                                             984


<210>  31
<211>  1683
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CAR-p2A-IL15 construct

<400>  31
actagtgcca ccatggccag acctcatcct tggtggctgt gtgtgctggg cacactcgtt       60

ggcctgtctg ctacaccagc tcctaagagc tgccccgaga gacactattg ggcccagggc      120

aagctgtgct gccagatgtg tgaacctggc accttcctgg tcaaggactg cgaccagcac      180

agaaaggccg ctcagtgcga tccttgtatc cccggcgtgt ccttctctcc cgaccaccac      240

acaagacctc actgcgagag ctgcagacac tgcaattctg gactgctcgt gcggaactgc      300

accatcacag ccaatgccga gtgcgcctgc agaaatggct ggcagtgccg ggacaaagaa      360

tgtaccgagt gcgaccctct gcctaatcct agcctgaccg ccagaagcag ccaggctttg      420

tctcctcatc ctcagcctac acatctgccc tacgtgtccg agatgctgga agccagaaca      480

gccggccata tgcagaccct ggccgacttt agacagctgc ccgccagaac actgagcacc      540

cattggcctc cacagagaag cctgtgcagc agcgacttca tccggatcct cgtgatcttc      600

agcggcatgt tcctggtgtt cacactggct ggcgccctgt ttctgcataa gcgcggtcgg      660

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag      720

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg      780

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac      840

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac      900

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc      960

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga     1020

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac     1080

gctcttcaca tgcaggccct gccgcctcgg gaattcggat ctggcgccac caatttcagc     1140

ctgctgaaac aggctggcga cgtggaagag aaccctggac ctatgagaat cagcaagccc     1200

cacctgagat ccatcagcat ccagtgctac ctgtgcctgc tgctgaacag ccactttctg     1260

acagaggccg gcatccacgt gttcatcctg ggctgttttt ctgccggcct gcctaagacc     1320

gaggccaact gggttaacgt gatcagcgac ctgaagaaga tcgaggacct gatccagagc     1380

atgcacatcg acgccacact gtacaccgag agcgacgtgc accctagctg taaagtgacc     1440

gccatgaagt gctttctgct ggaactgcaa gtgatcagcc tggaaagcgg cgacgccagc     1500

atccacgaca ccgtggaaaa cctgatcatc ctggccaaca acagcctgag cagcaacggc     1560

aatgtgaccg agtccggctg caaagagtgc gaggaactgg aagagaagaa tatcaaagag     1620

ttcctgcaga gcttcgtgca catcgtgcag atgttcatca acaccagcga attctaactc     1680

gag                                                                   1683


<210>  32
<211>  554
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CAR-P2A-IL21 polypeptide

<400>  32

Met Ala Arg Pro His Pro Trp Trp Leu Cys Val Leu Gly Thr Leu Val 
1               5                   10                  15      


Gly Leu Ser Ala Thr Pro Ala Pro Lys Ser Cys Pro Glu Arg His Tyr 
            20                  25                  30          


Trp Ala Gln Gly Lys Leu Cys Cys Gln Met Cys Glu Pro Gly Thr Phe 
        35                  40                  45              


Leu Val Lys Asp Cys Asp Gln His Arg Lys Ala Ala Gln Cys Asp Pro 
    50                  55                  60                  


Cys Ile Pro Gly Val Ser Phe Ser Pro Asp His His Thr Arg Pro His 
65                  70                  75                  80  


Cys Glu Ser Cys Arg His Cys Asn Ser Gly Leu Leu Val Arg Asn Cys 
                85                  90                  95      


Thr Ile Thr Ala Asn Ala Glu Cys Ala Cys Arg Asn Gly Trp Gln Cys 
            100                 105                 110         


Arg Asp Lys Glu Cys Thr Glu Cys Asp Pro Leu Pro Asn Pro Ser Leu 
        115                 120                 125             


Thr Ala Arg Ser Ser Gln Ala Leu Ser Pro His Pro Gln Pro Thr His 
    130                 135                 140                 


Leu Pro Tyr Val Ser Glu Met Leu Glu Ala Arg Thr Ala Gly His Met 
145                 150                 155                 160 


Gln Thr Leu Ala Asp Phe Arg Gln Leu Pro Ala Arg Thr Leu Ser Thr 
                165                 170                 175     


His Trp Pro Pro Gln Arg Ser Leu Cys Ser Ser Asp Phe Ile Arg Ile 
            180                 185                 190         


Leu Val Ile Phe Ser Gly Met Phe Leu Val Phe Thr Leu Ala Gly Ala 
        195                 200                 205             


Leu Phe Leu His Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys 
    210                 215                 220                 


Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys 
225                 230                 235                 240 


Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val 
                245                 250                 255     


Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn 
            260                 265                 270         


Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val 
        275                 280                 285             


Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg 
    290                 295                 300                 


Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys 
305                 310                 315                 320 


Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg 
                325                 330                 335     


Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys 
            340                 345                 350         


Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg Glu Phe 
        355                 360                 365             


Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val 
    370                 375                 380                 


Glu Glu Asn Pro Gly Pro Met Arg Ser Ser Pro Gly Asn Met Glu Arg 
385                 390                 395                 400 


Ile Val Ile Cys Leu Met Val Ile Phe Leu Gly Thr Leu Val His Lys 
                405                 410                 415     


Ser Ser Ser Gln Gly Gln Asp Arg His Met Ile Arg Met Arg Gln Leu 
            420                 425                 430         


Ile Asp Ile Val Asp Gln Leu Lys Asn Tyr Val Asn Asp Leu Val Pro 
        435                 440                 445             


Glu Phe Leu Pro Ala Pro Glu Asp Val Glu Thr Asn Cys Glu Trp Ser 
    450                 455                 460                 


Ala Phe Ser Cys Phe Gln Lys Ala Gln Leu Lys Ser Ala Asn Thr Gly 
465                 470                 475                 480 


Asn Asn Glu Arg Ile Ile Asn Val Ser Ile Lys Lys Leu Lys Arg Lys 
                485                 490                 495     


Pro Pro Ser Thr Asn Ala Gly Arg Arg Gln Lys His Arg Leu Thr Cys 
            500                 505                 510         


Pro Ser Cys Asp Ser Tyr Glu Lys Lys Pro Pro Lys Glu Phe Leu Glu 
        515                 520                 525             


Arg Phe Lys Ser Leu Leu Gln Lys Met Ile His Gln His Leu Ser Ser 
    530                 535                 540                 


Arg Thr His Gly Ser Glu Asp Ser Glu Phe 
545                 550                 


<210>  33
<211>  1683
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CAR-P2A-IL21 construct

<400>  33
actagtgcca ccatggccag acctcatcct tggtggctgt gtgtgctggg cacactcgtt       60

ggcctgtctg ctacaccagc tcctaagagc tgccccgaga gacactattg ggcccagggc      120

aagctgtgct gccagatgtg tgaacctggc accttcctgg tcaaggactg cgaccagcac      180

agaaaggccg ctcagtgcga tccttgtatc cccggcgtgt ccttctctcc cgaccaccac      240

acaagacctc actgcgagag ctgcagacac tgcaattctg gactgctcgt gcggaactgc      300

accatcacag ccaatgccga gtgcgcctgc agaaatggct ggcagtgccg ggacaaagaa      360

tgtaccgagt gcgaccctct gcctaatcct agcctgaccg ccagaagcag ccaggctttg      420

tctcctcatc ctcagcctac acatctgccc tacgtgtccg agatgctgga agccagaaca      480

gccggccata tgcagaccct ggccgacttt agacagctgc ccgccagaac actgagcacc      540

cattggcctc cacagagaag cctgtgcagc agcgacttca tccggatcct cgtgatcttc      600

agcggcatgt tcctggtgtt cacactggct ggcgccctgt ttctgcataa gcgcggtcgg      660

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag      720

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg      780

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac      840

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac      900

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc      960

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga     1020

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac     1080

gctcttcaca tgcaggccct gccgcctcgg gaattcggat ctggcgccac caatttcagc     1140

ctgctgaaac aggctggcga cgtggaagag aaccctggac ctatgagatc cagtcctggc     1200

aacatggaga ggattgtcat ctgtctgatg gtcatcttct tggggacact ggtccacaaa     1260

tcaagctccc aaggtcaaga tcgccacatg attagaatgc gtcaacttat agatattgtt     1320

gatcagctga aaaattatgt gaatgacttg gtccctgaat ttctgccagc tccagaagat     1380

gtagagacaa actgtgagtg gtcagctttt tcctgctttc agaaggccca actaaagtca     1440

gcaaatacag gaaacaatga aaggataatc aatgtatcaa ttaaaaagct gaagaggaaa     1500

ccaccttcca caaatgcagg gagaagacag aaacacagac taacatgccc ttcatgtgat     1560

tcttatgaga aaaaaccacc caaagaattc ctagaaagat tcaaatcact tctccaaaag     1620

atgattcatc agcatctgtc ctctagaaca cacggaagtg aagattccga attctaactc     1680

gag                                                                   1683


<210>  34
<211>  961
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CAR-P2A-IL12 polypeptide

<400>  34

Met Ala Arg Pro His Pro Trp Trp Leu Cys Val Leu Gly Thr Leu Val 
1               5                   10                  15      


Gly Leu Ser Ala Thr Pro Ala Pro Lys Ser Cys Pro Glu Arg His Tyr 
            20                  25                  30          


Trp Ala Gln Gly Lys Leu Cys Cys Gln Met Cys Glu Pro Gly Thr Phe 
        35                  40                  45              


Leu Val Lys Asp Cys Asp Gln His Arg Lys Ala Ala Gln Cys Asp Pro 
    50                  55                  60                  


Cys Ile Pro Gly Val Ser Phe Ser Pro Asp His His Thr Arg Pro His 
65                  70                  75                  80  


Cys Glu Ser Cys Arg His Cys Asn Ser Gly Leu Leu Val Arg Asn Cys 
                85                  90                  95      


Thr Ile Thr Ala Asn Ala Glu Cys Ala Cys Arg Asn Gly Trp Gln Cys 
            100                 105                 110         


Arg Asp Lys Glu Cys Thr Glu Cys Asp Pro Leu Pro Asn Pro Ser Leu 
        115                 120                 125             


Thr Ala Arg Ser Ser Gln Ala Leu Ser Pro His Pro Gln Pro Thr His 
    130                 135                 140                 


Leu Pro Tyr Val Ser Glu Met Leu Glu Ala Arg Thr Ala Gly His Met 
145                 150                 155                 160 


Gln Thr Leu Ala Asp Phe Arg Gln Leu Pro Ala Arg Thr Leu Ser Thr 
                165                 170                 175     


His Trp Pro Pro Gln Arg Ser Leu Cys Ser Ser Asp Phe Ile Arg Ile 
            180                 185                 190         


Leu Val Ile Phe Ser Gly Met Phe Leu Val Phe Thr Leu Ala Gly Ala 
        195                 200                 205             


Leu Phe Leu His Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys 
    210                 215                 220                 


Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys 
225                 230                 235                 240 


Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val 
                245                 250                 255     


Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn 
            260                 265                 270         


Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val 
        275                 280                 285             


Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg 
    290                 295                 300                 


Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys 
305                 310                 315                 320 


Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg 
                325                 330                 335     


Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys 
            340                 345                 350         


Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg Glu Phe 
        355                 360                 365             


Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val 
    370                 375                 380                 


Glu Glu Asn Pro Gly Pro Met Cys Pro Ala Arg Ser Leu Leu Leu Val 
385                 390                 395                 400 


Ala Thr Leu Val Leu Leu Asp His Leu Ser Leu Ala Arg Asn Leu Pro 
                405                 410                 415     


Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys Leu His His Ser Gln 
            420                 425                 430         


Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln Lys Ala Arg Gln Thr 
        435                 440                 445             


Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile Asp His Glu Asp Ile 
    450                 455                 460                 


Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys Leu Pro Leu Glu Leu 
465                 470                 475                 480 


Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu Thr Ser Phe Ile Thr 
                485                 490                 495     


Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser Phe Met Met Ala Leu 
            500                 505                 510         


Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met Tyr Gln Val Glu Phe 
        515                 520                 525             


Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro Lys Arg Gln Ile Phe 
    530                 535                 540                 


Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu Leu Met Gln Ala Leu 
545                 550                 555                 560 


Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser Ser Leu Glu Glu Pro 
                565                 570                 575     


Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile Leu Leu His Ala Phe 
            580                 585                 590         


Arg Ile Arg Ala Val Thr Ile Asp Arg Val Met Ser Tyr Leu Asn Ala 
        595                 600                 605             


Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp 
    610                 615                 620                 


Val Glu Glu Asn Pro Gly Pro Met Cys His Gln Gln Leu Val Ile Ser 
625                 630                 635                 640 


Trp Phe Ser Leu Val Phe Leu Ala Ser Pro Leu Val Ala Ile Trp Glu 
                645                 650                 655     


Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr Pro Asp Ala 
            660                 665                 670         


Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu Glu Asp Gly 
        675                 680                 685             


Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly Ser Gly Lys 
    690                 695                 700                 


Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly Gln Tyr Thr 
705                 710                 715                 720 


Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu Leu Leu His 
                725                 730                 735     


Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys Asp Gln Lys 
            740                 745                 750         


Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys Asn Tyr Ser 
        755                 760                 765             


Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr Asp Leu Thr 
    770                 775                 780                 


Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln Gly Val Thr 
785                 790                 795                 800 


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


Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala Cys Pro Ala 
            820                 825                 830         


Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala Val His Lys 
        835                 840                 845             


Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg Asp Ile Ile 
    850                 855                 860                 


Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu Lys Asn Ser 
865                 870                 875                 880 


Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp Ser Thr Pro 
                885                 890                 895     


His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln Gly Lys Ser 
            900                 905                 910         


Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr Ser Ala Thr 
        915                 920                 925             


Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala Gln Asp Arg 
    930                 935                 940                 


Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro Cys Ser Glu 
945                 950                 955                 960 


Phe 
    


<210>  35
<211>  2904
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CAR-P2A-IL12 construct

<400>  35
actagtgcca ccatggccag acctcatcct tggtggctgt gtgtgctggg cacactcgtt       60

ggcctgtctg ctacaccagc tcctaagagc tgccccgaga gacactattg ggcccagggc      120

aagctgtgct gccagatgtg tgaacctggc accttcctgg tcaaggactg cgaccagcac      180

agaaaggccg ctcagtgcga tccttgtatc cccggcgtgt ccttctctcc cgaccaccac      240

acaagacctc actgcgagag ctgcagacac tgcaattctg gactgctcgt gcggaactgc      300

accatcacag ccaatgccga gtgcgcctgc agaaatggct ggcagtgccg ggacaaagaa      360

tgtaccgagt gcgaccctct gcctaatcct agcctgaccg ccagaagcag ccaggctttg      420

tctcctcatc ctcagcctac acatctgccc tacgtgtccg agatgctgga agccagaaca      480

gccggccata tgcagaccct ggccgacttt agacagctgc ccgccagaac actgagcacc      540

cattggcctc cacagagaag cctgtgcagc agcgacttca tccggatcct cgtgatcttc      600

agcggcatgt tcctggtgtt cacactggct ggcgccctgt ttctgcataa gcgcggtcgg      660

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag      720

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg      780

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac      840

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac      900

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc      960

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga     1020

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac     1080

gctcttcaca tgcaggccct gccgcctcgg gaattcggat ctggcgccac caatttcagc     1140

ctgctgaaac aggctggcga cgtggaagag aaccctggac ctatgtgtcc agcgcgcagc     1200

ctcctccttg tggctaccct ggtcctcctg gaccacctca gtttggccag aaacctcccc     1260

gtggccactc cagacccagg aatgttccca tgccttcacc actcccaaaa cctgctgagg     1320

gccgtcagca acatgctcca gaaggccaga caaactctag aattttaccc ttgcacttct     1380

gaagagattg atcatgaaga tatcacaaaa gataaaacca gcacagtgga ggcctgttta     1440

ccattggaat taaccaagaa tgagagttgc ctaaattcca gagagacctc tttcataact     1500

aatgggagtt gcctggcctc cagaaagacc tcttttatga tggccctgtg ccttagtagt     1560

atttatgaag acttgaagat gtaccaggtg gagttcaaga ccatgaatgc aaagcttctg     1620

atggatccta agaggcagat ctttctagat caaaacatgc tggcagttat tgatgagctg     1680

atgcaggccc tgaatttcaa cagtgagact gtgccacaaa aatcctccct tgaagaaccg     1740

gatttttata aaactaaaat caagctctgc atacttcttc atgctttcag aattcgggca     1800

gtgactattg atagagtgat gagctatctg aatgcttccg gatctggcgc caccaatttc     1860

agcctgctga aacaggctgg cgacgtggaa gagaaccctg gacctatgtg tcaccagcag     1920

ttggtcatct cttggttttc cctggttttt ctggcatctc ccctcgtggc catatgggaa     1980

ctgaagaaag atgtttatgt cgtagaattg gattggtatc cggatgcccc tggagaaatg     2040

gtggtcctca cctgtgacac ccctgaagaa gatggtatca cctggacctt ggaccagagc     2100

agtgaggtct taggctctgg caaaaccctg accatccaag tcaaagagtt tggagatgct     2160

ggccagtaca cctgtcacaa aggaggcgag gttctaagcc attcgctcct gctgcttcac     2220

aaaaaggaag atggaatttg gtccactgat attttaaagg accagaaaga acccaaaaat     2280

aagacctttc taagatgcga ggccaagaat tattctggac gtttcacctg ctggtggctg     2340

acgacaatca gtactgattt gacattcagt gtcaaaagca gcagaggctc ttctgacccc     2400

caaggggtga cgtgcggagc tgctacactc tctgcagaga gagtcagagg ggacaacaag     2460

gagtatgagt actcagtgga gtgccaggag gacagtgcct gcccagctgc tgaggagagt     2520

ctgcccattg aggtcatggt ggatgccgtt cacaagctca agtatgaaaa ctacaccagc     2580

agcttcttca tcagggacat catcaaacct gacccaccca agaacttgca gctgaagcca     2640

ttaaagaatt ctcggcaggt ggaggtcagc tgggagtacc ctgacacctg gagtactcca     2700

cattcctact tctccctgac attctgcgtt caggtccagg gcaagagcaa gagagaaaag     2760

aaagatagag tcttcacgga caagacctca gccacggtca tctgccgcaa aaatgccagc     2820

attagcgtgc gggcccagga ccgctactat agctcatctt ggagcgaatg ggcatctgtg     2880

ccctgcagtg aattctaact cgag                                            2904


