序列表 

<110>  南京北恒生物科技有限公司
 
<120>  包含新型共刺激结构域的嵌合抗原受体及其用途

<130>  BHCN26

<160>  44  

<170>  PatentIn version 3.5

<210>  1
<211>  242
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  CD19 scFv-1

<400>  1
Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly
                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>  2
<211>  726
<212>  DNA
<213>  Artificial Sequence

<220>
<221>
<223>  CD19 scFv-1

<400>  2
gacatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagagtcacc    60

atcagttgca gggcaagtca ggacattagt aaatatttaa attggtatca gcagaaacca    120

gatggaactg ttaaactcct gatctaccat acatcaagat tacactcagg agtcccatca    180

aggttcagtg gcagtgggtc tggaacagat tattctctca ccattagcaa cctggagcaa    240

gaagatattg ccacttactt ttgccaacag ggtaatacgc ttccgtacac gttcggaggg    300

gggaccaagc tggagatcac aggtggcggt ggctcgggcg gtggtgggtc gggtggcggc    360

ggatctgagg tgaaactgca ggagtcagga cctggcctgg tggcgccctc acagagcctg    420

tccgtcacat gcactgtctc aggggtctca ttacccgact atggtgtaag ctggattcgc    480

cagcctccac gaaagggtct ggagtggctg ggagtaatat ggggtagtga aaccacatac    540

tataattcag ctctcaaatc cagactgacc atcatcaagg acaactccaa gagccaagtt    600

ttcttaaaaa tgaacagtct gcaaactgat gacacagcca tttactactg tgccaaacat    660

tattactacg gtggtagcta tgctatggac tactggggcc aaggaacctc agtcaccgtc    720

tcctca                                                               726


<210>  3
<211>  25
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  CD8α跨膜结构域

<400>  3
Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu 
                5                   10                  15

Ser Leu Val Ile Thr Leu Tyr Cys Lys
            20                  25


<210>  4
<211>  75
<212>  DNA
<213>  Artificial Sequence

<220>
<221>
<223>  CD8α跨膜结构域

<400>  4
atctacatct gggcgccctt ggccgggact tgtggggtcc ttctcctgtc actggttatc     60

accctttact gcaaa                                                      75


<210>  5
<211>  27
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  CD28跨膜结构域

<400>  5
Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu
                5                   10                  15

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


<210>  6
<211>  81
<212>  DNA
<213>  Artificial Sequence

<220>
<221>
<223>  CD28跨膜结构域

<400>  6
ttttgggtcc tcgtcgtagt tggaggggta cttgcctgtt atagcctcct ggttaccgta     60

gcatttatta tattctgggt g                                               81


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

<220>
<221>
<223>  CD28胞内区

<400>  7
Arg Ser Lys Arg Ser Arg Leu Leu His Ser Asp Tyr Met Asn Met Thr 
                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>  123
<212>  DNA
<213>  Artificial Sequence

<220>
<221>
<223>  CD28胞内区

<400>  8
aggagtaaga ggagcaggct cctgcacagt gactacatga acatgactcc ccgccgcccc     60

gggcccaccc gcaagcatta ccagccctat gccccaccac gcgacttcgc agcctatcgc    120

tcc                                                                  123


<210>  9
<211>  40
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  4-1BB胞内区

<400>  9
Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg 
                5                   10                  15

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

Glu Glu Glu Glu Gly Gly Cys Glu
        35                  40


<210>  10
<211>  120
<212>  DNA
<213>  Artificial Sequence

<220>
<221>
<223>  4-1BB胞内区

<400>  10
cggggcagaa agaaactcct gtatatattc aaacaaccat ttatgagacc agtacaaact     60

actcaagagg aagatggctg tagctgccga tttccagaag aagaagaagg aggatgtgaa     120


<210>  11
<211>  113
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  CD3ζ胞内区

<400>  11
Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln 
                5                   10                  15

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

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

Lys Pro 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>  12
<211>  339
<212>  DNA
<213>  Artificial Sequence

<220>
<221>
<223>  CD3ζ胞内区

<400>  12
ctgagagtga agttcagcag gagcgcagac gcccccgcgt accagcaggg ccagaaccag     60

ctctataacg agctcaatct aggacgaaga gaggagtacg atgttttgga caagagacgt    120

ggccgggacc ctgagatggg gggaaagccg agaaggaaga accctcagga aggcctgtac    180

aatgaactgc agaaagataa gatggcggag gcctacagtg agattgggat gaaaggcgag    240

cgccggaggg gcaaggggca cgatggcctt taccagggtc tcagtacagc caccaaggac    300

acctacgacg cccttcacat gcaggccctg ccccctcgc                           339


<210>  13
<211>  114
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  CD3ζ胞内区

<400>  13
Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln
                5                   10                  15

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

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

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

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

Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Phe Gln Gly Leu Ser
                85                  90                  95

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


<210>  14
<211>  342
<212>  DNA
<213>  Artificial Sequence

<220>
<221>
<223>  CD3ζ胞内区

<400>  14
ctgagagtga agttcagcag gagcgcagac gcccccgcgt accagcaggg ccagaaccag     60

ctctttaacg agctcaatct aggacgaaga gaggagttcg atgttttgga caagagacgt    120

ggccgggacc ctgagatggg gggaaagccg cagagaagga agaaccctca ggaaggcctg    180

tacaatgaac tgcagaaaga taagatggcg gaggcctaca gtgagattgg gatgaaaggc    240

gagcgccgga ggggcaaggg gcacgatggc cttttccagg gtctcagtac agccaccaag    300

gacacctttg acgcccttca catgcaggcc ctgccccctc gc                       342


<210>  15
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  B2M信号肽

<400>  15
Met Ser Arg Ser Val Ala Leu Ala Val Leu Ala Leu Leu Ser Leu Ser
                5                   10                  15

Gly Leu Glu Ala
            20


<210>  16
<211>  60
<212>  DNA
<213>  Artificial Sequence

<220>
<221>
<223>  B2M信号肽

<400>  16
atgtcccgct ctgttgcttt ggctgtgctg gcccttttgt cccttagcgg actggaggcc     60


<210>  17
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  CD8α信号肽

<400>  17
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu
                5                   10                  15

His Ala Ala Arg Pro
            20


<210>  18
<211>  63
<212>  DNA
<213>  Artificial Sequence

<220>
<221>
<223>  CD8α信号肽

<400>  18
atggccttac cagtgaccgc cttgctcctg ccgctggcct tgctgctcca cgccgccagg     60

ccg                                                                   63


<210>  19
<211>  45
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  CD8α铰链区

<400>  19
Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala
                5                   10                  15

Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly
            20                  25                  30

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


<210>  20
<211>  135
<212>  DNA
<213>  Artificial Sequence

<220>
<221>
<223>  CD8α铰链区

<400>  20
accacgacgc cagcgccgcg accaccaaca ccggcgccca ccatcgcgtc gcagcccctg     60

tccctgcgcc cagaggcgtg ccggccagcg gcggggggcg cagtgcacac gagggggctg    120

gacttcgcct gtgat                                                     135


<210>  21
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  CD28铰链区

<400>  21
Ile Glu Val Met Tyr Pro Pro Pro Tyr Leu Asp Asn Glu Lys Ser Asn
                5                   10                  15

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

Phe Pro Gly Pro Ser Lys Pro
        35


<210>  22
<211>  117
<212>  DNA
<213>  Artificial Sequence

<220>
<221>
<223>  CD28铰链区

<400>  22
attgaagtta tgtatcctcc tccttaccta gacaatgaga agagcaatgg aaccattatc     60

catgtgaaag ggaaacacct ttgtccaagt cccctatttc ccggaccttc taagccc       117


<210>  23
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  IgG4铰链区

<400>  23
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro
                5                   10


<210>  24
<211>  36
<212>  DNA
<213>  Artificial Sequence

<220>
<221>
<223>  IgG4铰链区

<400>  24
gaaagcaaat acgggccgcc gtgtccaccc tgtccg                               36


<210>  25
<211>  238
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  CD19 scFv-2

<400>  25
Asp Ile Gln Met Thr Gln Ser Pro Ala Ser Leu Ser Thr Ser Leu Gly 
                5                   10                  15

Glu Thr Val Thr Ile Gln Cys Gln Ala Ser Glu Asp Ile Tyr Ser Gly
            20                  25                  30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ser Pro Gln Leu Leu Ile
        35                  40                  45

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

Ser Gly Ser Gly Thr Gln Tyr Ser Leu Lys Ile Thr Ser Met Gln Thr
65                  70                  75                  80

Glu Asp Glu Gly Val Tyr Phe Cys Gln Gln Gly Leu Thr Tyr Pro Arg
                85                  90                  95

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

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

Ser Gly Ala Glu Leu Val Arg Pro Gly Thr Ser Val Lys Leu Ser Cys
    130                 135                 140

Lys Val Ser Gly Asp Thr Ile Thr Phe Tyr Tyr Met His Phe Val Lys
145                 150                 155                 160

Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile Gly Arg Ile Asp Pro Glu
                165                 170                 175

Asp Glu Ser Thr Lys Tyr Ser Glu Lys Phe Lys Asn Lys Ala Thr Leu
            180                 185                 190

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

Thr Ser Glu Asp Thr Ala Thr Tyr Phe Cys Ile Tyr Gly Gly Tyr Tyr
    210                 215                 220

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


<210>  26
<211>  714
<212>  DNA
<213>  Artificial Sequence

<220>
<221>
<223>  CD19 scFv-2

<400>  26
gacatccaga tgacccagag ccctgccagc ctgtctacca gcctgggcga gacagtgacc     60

atccagtgtc aggccagcga ggacatctac tctggcctgg cttggtatca gcagaagccc    120 

ggcaagagcc ctcagctgct gatctacggc gccagcgacc tgcaggacgg cgtgcctagc    180

agattcagcg gcagcggctc cggaacccag tacagcctga agatcaccag catgcagacc    240

gaggacgagg gcgtgtactt ctgccagcaa ggcctgacct accctagaac cttcggagga    300 

ggcaccaagc tggaactgaa gggcggaggc ggaagtggag gcggaggatc tggcggcgga    360

ggctctgaag tgcagctgca gcagtctggc gctgaactgg tccggcctgg cactagcgtg    420

aagctgtcct gcaaggtgtc cggcgacacc atcaccttct actacatgca cttcgtgaag    480

cagaggccag gacagggcct ggaatggatc ggcagaatcg accctgagga cgagagcacc    540

aagtacagcg agaagttcaa gaacaaggcc accctgaccg ccgacaccag cagcaacacc    600

gcctacctga agctgtctag cctgacctcc gaggacaccg ccacctactt ttgcatctac    660

ggcggctact acttcgacta ctggggccag ggcgtgatgg tcaccgtgtc cagc          714


<210>  27
<211>  37
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  ICAM3胞内区

<400>  27
Arg Glu His Gln Arg Ser Gly Ser Tyr His Val Arg Glu Glu Ser Thr
                5                   10                  15
 
Tyr Leu Pro Leu Thr Ser Met Gln Pro Thr Glu Ala Met Gly Glu Glu
            20                  25                  30

Pro Ser Arg Ala Glu
        35


<210>  28
<211>  111
<212>  DNA
<213>  Artificial Sequence

<220>
<221>
<223>  ICAM3胞内区

<400>  28
cgcgaacacc agagatcagg gtcttaccac gtaagagaag aaagtaccta ccttcctttg     60

acaagtatgc agccaacgga ggctatgggt gaggaacctt ccagagcgga a             111


<210>  29
<211>  50
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  CD155胞内区

<400>  29
Ser Lys Cys Ser Arg Glu Val Leu Trp His Cys His Leu Cys Pro Ser
                5                   10                  15
 
Ser Thr Glu His Ala Ser Ala Ser Ala Asn Gly His Val Ser Tyr Ser
            20                  25                  30

Ala Val Ser Arg Glu Asn Ser Ser Ser Gln Asp Pro Gln Thr Glu Gly
        35                  40                  45

Thr Arg
    50


<210>  30
<211>  150
<212>  DNA
<213>  Artificial Sequence

<220>
<221>
<223>  CD155胞内区

<400>  30
tccaaatgtt cccgtgaggt cctttggcac tgtcatctgt gtccctcgag tacagagcat     60

gccagcgcct cagctaatgg gcatgtctcc tattcagctg tgagcagaga gaacagctct    120

tcccaggatc cacagacaga gggcacaagg                                     150


<210>  31
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  2B4胞内区

<400>  31
Arg Lys Arg Lys Glu Lys Gln Ser Glu Thr Ser Pro Lys Glu Phe Leu
                5                   10                  15

Thr Ile Tyr Glu Asp Val Lys Asp Leu Lys Thr Arg Arg Asn His Glu
            20                  25                  30

Gln Glu Gln Thr Phe Pro Gly Gly Gly Ser Thr Ile Tyr Ser Met Ile
        35                  40                  45

Gln Ser Gln Ser Ser Ala Pro Thr Ser Gln Glu Pro Ala Tyr Thr Leu
    50                  55                  60

Tyr Ser Leu Ile Gln Pro Ser Arg Lys Ser Gly Ser Arg Lys Arg Asn
65                  70                  75                  80

His Ser Pro Ser Phe Asn Ser Thr Ile Tyr Glu Val Ile Gly Lys Ser
                85                  90                  95

Gln Pro Lys Ala Gln Asn Pro Ala Arg Leu Ser Arg Lys Glu Leu Glu
            100                 105                 110

Asn Phe Asp Val Tyr Ser
        115


<210>  32
<211>  354
<212>  DNA
<213>  Artificial Sequence

<220>
<221>
<223>  2B4胞内区

<400>  32
agaaagagga aggagaagca gtcagagacc agtcccaagg aatttttgac aatttacgaa     60

gatgtcaagg atctgaaaac caggagaaat cacgagcagg agcagacttt tcctggaggg    120

gggagcacca tctactctat gatccagtcc cagtcttctg ctcccacgtc acaagaacct    180

gcatatacat tatattcatt aattcagcct tccaggaagt ctggatccag gaagaggaac    240

cacagccctt ccttcaatag cactatctat gaagtgattg gaaagagtca acctaaagcc    300

cagaaccctg ctcgattgag ccgcaaagag ctggagaact ttgatgttta ttcc          354


<210>  33
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  CD19 scFv-1 CDR-L1

<400>  33
Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn
                5                   10


<210>  34
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  CD19 scFv-1 CDR-L2

<400>  34
His Thr Ser Arg Leu His Ser
                5


<210>  35
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  CD19 scFv-1 CDR-L3

<400>  35
Gln Gln Gly Asn Thr Leu Pro Tyr Thr
                5


<210>  36
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  CD19 scFv-1 CDR-H1

<400>  36
Gly Val Ser Leu Pro Asp Tyr
                5


<210>  37
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  CD19 scFv-1 CDR-H2

<400>  37
Trp Gly Ser Glu Thr
                5


<210>  38
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  CD19 scFv-1 CDR-H3

<400>  38
His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr
                5                   10


<210>  39
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  CD19 scFv-2 CDR-L1

<400>  39
Gln Ala Ser Glu Asp Ile Tyr Ser Gly Leu Ala
                5                   10


<210>  40
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  CD19 scFv-2 CDR-L2

<400>  40
Gly Ala Ser Asp Leu Gln Asp
                5


<210>  41
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  CD19 scFv-2 CDR-L3

<400>  41
Gln Gln Gly Leu Thr Tyr Pro Arg Thr
                5


<210>  42
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  CD19 scFv-2 CDR-H1

<400>  42
Gly Asp Thr Ile Thr Phe Tyr
                5


<210>  43
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  CD19 scFv-2 CDR-H2

<400>  43
Asp Pro Glu Asp Glu Ser
                5


<210>  44
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<221>
<223>  CD19 scFv-2 CDR-H3

<400>  44
Gly Gly Tyr Tyr Phe Asp Tyr
                5



