                         б

<110>  ϾƼ޹˾
 
<120>  Tϸںϵ׼;

<130>  BHCN13

<160>  40    

<170>  PatentIn version 3.5

<210>  1
<211>  24
<212>  DNA
<213>  ˹

<220>
<223>  TRAC sgRNA

<400>  1
atagagagtc tctcagctgg taca                                            24                                            


<210>  2
<211>  20
<212>  DNA
<213>  ˹

<220>
<223>  TRBC sgRNA

<400>  2
ggagaatgac gagtggaccc                                                 20                                          


<210>  3
<211>  360
<212>  DNA
<213>  ˹

<220>
<223>  CD19 scFv-VH

<400>  3
gaggtgaaac tgcaggagtc aggacctggc ctggtggcgc cctcacagag cctgtccgtc     60

acatgcactg tctcaggggt ctcattaccc gactatggtg taagctggat tcgccagcct    120

ccacgaaagg gtctggagtg gctgggagta atatggggta gtgaaaccac atactataat    180

tcagctctca aatccagact gaccatcatc aaggacaact ccaagagcca agttttctta    240

aaaatgaaca gtctgcaaac tgatgacaca gccatttact actgtgccaa acattattac    300

tacggtggta gctatgctat ggactactgg ggccaaggaa cctcagtcac cgtctcctca    360


<210>  4
<211>  120
<212>  PRT
<213>  ˹

<220>
<223>  CD19 scFv-VH

<400>  4
Glu Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln  
                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>  5
<211>  321
<212>  DNA
<213>  ˹

<220>
<223>  CD19 scFv-VL

<400>  5
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 a                                              321


<210>  6
<211>  107
<212>  PRT
<213>  ˹

<220>
<223>  CD19 scFv-VL

<400>  6
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
            100                 105


<210>  7
<211>  636
<212>  DNA
<213>  ˹

<220>
<223>  CD19 scFv-VL-CL

<400>  7
atccagatga cacagactac atcctccctg tctgcctctc tgggagacag agtcaccatc     60 

agttgcaggg caagtcagga cattagtaaa tatttaaatt ggtatcagca gaaaccagat    120

ggaactgtta aactcctgat ctaccataca tcaagattac actcaggagt cccatcaagg    180

ttcagtggca gtgggtctgg aacagattat tctctcacca ttagcaacct ggagcaagaa    240

gatattgcca cttacttttg ccaacagggt aatacgcttc cgtacacgtt cggagggggg    300

accaagctgg agatcacagg ccagcctaaa gcaaatccca ctgtaacact cttccctccc    360

agcagcgagg aattgcaggc caacaaagca acacttgtgt gtctgatctc cgacttttac    420

cctggagccg taaccgtagc ctggaaggcc gatggctccc cagttaaagc aggtgtagaa    480

actacaaagc catccaaaca gtccaacaat aagtatgcag cttcaagtta tctctcactt    540

acccccgagc aatggaagtc tcataggtcc tactcctgtc aagttaccca tgaggggtcc    600

acagtagaaa agacggtagc accgacggaa tgtagc                              636


<210>  8
<211>  213
<212>  PRT
<213>  ˹

<220>
<223>  CD19 scFv-VL-CL

<400>  8
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 Gln Pro Lys Ala
            100                 105                 110

Asn Pro Thr Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala 
        115                 120                 125

Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala 
    130                 135                 140

Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro Val Lys Ala Gly Val 
145                 150                 155                 160

Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser 
                165                 170                 175

Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Arg Ser Tyr 
            180                 185                 190

Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala 
        195                 200                 205

Pro Thr Glu Cys Ser
    210


<210>  9
<211>  669
<212>  DNA
<213>  ˹

<220>
<223>  CD19 scFv-VH-CH1

<400>  9
gaggtgaaac tgcaggagtc aggacctggc ctggtggcgc cctcacagag cctgtccgtc     60

acatgcactg tctcaggggt ctcattaccc gactatggtg taagctggat tcgccagcct    120

ccacgaaagg gtctggagtg gctgggagta atatggggta gtgaaaccac atactataat    180

tcagctctca aatccagact gaccatcatc aaggacaact ccaagagcca agttttctta    240

aaaatgaaca gtctgcaaac tgatgacaca gccatttact actgtgccaa acattattac    300

tacggtggta gctatgctat ggactactgg ggccaaggaa cctcagtcac cgtctcctca    360

gcgtccacga aggggccttc cgtatttcca ctggcaccct cttctaaatc aacgtctggg    420

ggtacggcag cgctcgggtg cctcgtgaaa gattacttcc cagaacctgt gacagtgtca    480

tggaacagtg gggcacttac atcaggcgtt catacttttc cagcagtgtt gcaatcaagc    540

ggactttatt ccctgtcatc cgttgtaacc gtaccttcaa gtagtttggg cacccagact    600

tacatctgca atgtaaacca taaaccgtct aataccaaag tggacaaaag ggttgaaccg    660

aagtcatgc                                                            669


<210>  10
<211>  223
<212>  PRT
<213>  ˹

<220>
<223>  CD19 scFv-VH-CH1

<400>  10
Glu Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln 
                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 Ala Ser Thr Lys Gly Pro Ser Val
        115                 120                 125

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 
    130                 135                 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
145                 150                 155                 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
                165                 170                 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
            180                 185                 190

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
        195                 200                 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys
    210                 215                 220

<210>  11
<211>  726
<212>  DNA
<213>  ˹

<220>
<223>  CD19 scFv

<400>  11
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>  12
<211>  242
<212>  PRT
<213>  ˹

<220>
<223>  CD19 scFv

<400>  12
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>  13
<211>  519
<212>  DNA
<213>  ˹

<220>
<223>  hTRGC

<400>  13
gacaagcagc tggacgccga cgtgagcccc aagcctacca tcttcctgcc cagcatcgcc     60

gagaccaagc tgcagaaggc cggcacctac ctgtgcctgc tggaaaagtt cttccccgac    120

gtgatcaaga tccactggga ggaaaagaag agcaacacca tcctgggcag ccaggaaggc    180

aataccatga aaaccaacga cacctacatg aagttcagct ggctgaccgt gcccgagaag    240

agcctggaca aagagcacag atgcatcgtc cggcacgaga acaacaagaa cggcgtggac    300

caggaaatca tcttcccccc catcaagacc gatgtgatca caatggaccc caaggacaac    360

tgcagcaagg acgccaacga taccctgctg ctgcagctga ccaacaccag cgcctactac    420

atgtatctcc tgctgctgct gaagagcgtg gtgtacttcg ccatcatcac ctgctgtctg    480

ctgcggcgga ccgccttctg ctgcaacggc gagaagagc                           519


<210>  14
<211>  173
<212>  PRT
<213>  ˹

<220>
<223>  hTRGC

<400>  14
Asp Lys Gln Leu Asp Ala Asp Val Ser Pro Lys Pro Thr Ile Phe Leu
                5                   10                  15

Pro Ser Ile Ala Glu Thr Lys Leu Gln Lys Ala Gly Thr Tyr Leu Cys
            20                  25                  30

Leu Leu Glu Lys Phe Phe Pro Asp Val Ile Lys Ile His Trp Glu Glu
        35                  40                  45

Lys Lys Ser Asn Thr Ile Leu Gly Ser Gln Glu Gly Asn Thr Met Lys
    50                  55                  60

Thr Asn Asp Thr Tyr Met Lys Phe Ser Trp Leu Thr Val Pro Glu Lys
65                  70                  75                  80

Ser Leu Asp Lys Glu His Arg Cys Ile Val Arg His Glu Asn Asn Lys
                85                  90                  95

Asn Gly Val Asp Gln Glu Ile Ile Phe Pro Pro Ile Lys Thr Asp Val
            100                 105                 110

Ile Thr Met Asp Pro Lys Asp Asn Cys Ser Lys Asp Ala Asn Asp Thr
        115                 120                 125

Leu Leu Leu Gln Leu Thr Asn Thr Ser Ala Tyr Tyr Met Tyr Leu Leu
    130                 135                 140

Leu Leu Leu Lys Ser Val Val Tyr Phe Ala Ile Ile Thr Cys Cys Leu
145                 150                 155                 160

Leu Arg Arg Thr Ala Phe Cys Cys Asn Gly Glu Lys Ser
                165                 170


<210>  15
<211>  459
<212>  DNA
<213>  ˹

<220>
<223>  hTRDC

<400>  15
agccagcccc acaccaagcc cagcgtgttc gtgatgaaga acggcaccaa cgtggcctgc     60

ctggtgaaag agttctaccc caaggacatc cggatcaacc tggtgtccag caagaagatc    120

accgagttcg accccgccat cgtgatcagc cccagcggca agtacaacgc cgtgaagctg    180

ggcaagtacg aggacagcaa cagcgtgacc tgcagcgtgc agcacgacaa caagaccgtg    240

cacagcaccg acttcgaggt gaaaaccgac tccaccgacc acgtgaagcc caaagagacc    300

gagaacacca agcagcccag caagagctgc cacaagccca aggccatcgt gcacaccgag    360

aaggtgaaca tgatgagcct gaccgtgctg ggcctgcgga tgctgttcgc caagacagtg    420

gccgtgaact tcctgctgac cgccaagctg ttcttcctg                           459


<210>  16
<211>  153
<212>  PRT
<213>  ˹

<220>
<223>  hTRDC

<400>  16
Ser Gln Pro His Thr Lys Pro Ser Val Phe Val Met Lys Asn Gly Thr
                5                   10                  15
 
Asn Val Ala Cys Leu Val Lys Glu Phe Tyr Pro Lys Asp Ile Arg Ile
            20                  25                  30

Asn Leu Val Ser Ser Lys Lys Ile Thr Glu Phe Asp Pro Ala Ile Val
        35                  40                  45

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

Asp Ser Asn Ser Val Thr Cys Ser Val Gln His Asp Asn Lys Thr Val
65                  70                  75                  80

His Ser Thr Asp Phe Glu Val Lys Thr Asp Ser Thr Asp His Val Lys
                85                  90                  95

Pro Lys Glu Thr Glu Asn Thr Lys Gln Pro Ser Lys Ser Cys His Lys
            100                 105                 110

Pro Lys Ala Ile Val His Thr Glu Lys Val Asn Met Met Ser Leu Thr
        115                 120                 125

Val Leu Gly Leu Arg Met Leu Phe Ala Lys Thr Val Ala Val Asn Phe
    130                 135                 140

Leu Leu Thr Ala Lys Leu Phe Phe Leu
145                 150


<210>  17
<211>  948
<212>  DNA
<213>  ˹

<220>
<223>  hTRG

<400>  17
atggtgtccc tgctgcacgc cagcaccctg gccgtgctgg gcgccctgtg cgtgtatggc     60

gccggacacc tggaacagcc ccagatcagc agcaccaaga ccctgagcaa gaccgccagg    120

ctggaatgcg tggtgtccgg catcaccatc agcgccacct ccgtgtactg gtacagagag    180

agacccggcg aggtcatcca gttcctggtg tccatcagct acgacggcac cgtgcggaaa    240

gagagcggca tccccagcgg caagttcgag gtggacagaa tccccgagac cagcacctcc    300

accctgacca tccacaacgt ggagaagcag gacatcgcca cctactactg cgccctgtgg    360

gaggcccagc aggaactggg caagaaaatc aaggtgttcg gccctggcac caagctgatc    420

atcaccgaca agcagctgga cgccgacgtg agccccaagc ctaccatctt cctgcccagc    480

atcgccgaga ccaagctgca gaaggccggc acctacctgt gcctgctgga aaagttcttc    540

cccgacgtga tcaagatcca ctgggaggaa aagaagagca acaccatcct gggcagccag    600

gaaggcaata ccatgaaaac caacgacacc tacatgaagt tcagctggct gaccgtgccc    660

gagaagagcc tggacaaaga gcacagatgc atcgtccggc acgagaacaa caagaacggc    720

gtggaccagg aaatcatctt cccccccatc aagaccgatg tgatcacaat ggaccccaag    780

gacaactgca gcaaggacgc caacgatacc ctgctgctgc agctgaccaa caccagcgcc    840

tactacatgt atctcctgct gctgctgaag agcgtggtgt acttcgccat catcacctgc    900

tgtctgctgc ggcggaccgc cttctgctgc aacggcgaga agagctga                 948


<210>  18
<211>  315
<212>  PRT
<213>  ˹

<220>
<223>  hTRG

<400>  18
Met Val Ser Leu Leu His Ala Ser Thr Leu Ala Val Leu Gly Ala Leu
                5                   10                  15
 
Cys Val Tyr Gly Ala Gly His Leu Glu Gln Pro Gln Ile Ser Ser Thr
            20                  25                  30

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

Thr Ile Ser Ala Thr Ser Val Tyr Trp Tyr Arg Glu Arg Pro Gly Glu
    50                  55                  60

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

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

Thr Ser Thr Ser Thr Leu Thr Ile His Asn Val Glu Lys Gln Asp Ile
            100                 105                 110

Ala Thr Tyr Tyr Cys Ala Leu Trp Glu Ala Gln Gln Glu Leu Gly Lys
        115                 120                 125

Lys Ile Lys Val Phe Gly Pro Gly Thr Lys Leu Ile Ile Thr Asp Lys
    130                 135                 140

Gln Leu Asp Ala Asp Val Ser Pro Lys Pro Thr Ile Phe Leu Pro Ser
145                 150                 155                 160

Ile Ala Glu Thr Lys Leu Gln Lys Ala Gly Thr Tyr Leu Cys Leu Leu
                165                 170                 175

Glu Lys Phe Phe Pro Asp Val Ile Lys Ile His Trp Glu Glu Lys Lys
            180                 185                 190

Ser Asn Thr Ile Leu Gly Ser Gln Glu Gly Asn Thr Met Lys Thr Asn
        195                 200                 205

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

Asp Lys Glu His Arg Cys Ile Val Arg His Glu Asn Asn Lys Asn Gly
225                 230                 235                 240

Val Asp Gln Glu Ile Ile Phe Pro Pro Ile Lys Thr Asp Val Ile Thr
                245                 250                 255

Met Asp Pro Lys Asp Asn Cys Ser Lys Asp Ala Asn Asp Thr Leu Leu
            260                 265                 270

Leu Gln Leu Thr Asn Thr Ser Ala Tyr Tyr Met Tyr Leu Leu Leu Leu
        275                 280                 285

Leu Lys Ser Val Val Tyr Phe Ala Ile Ile Thr Cys Cys Leu Leu Arg
    290                 295                 300

Arg Thr Ala Phe Cys Cys Asn Gly Glu Lys Ser
305                 310                 315

<210>  19
<211>  879
<212>  DNA
<213>  ˹

<220>
<223>  hTRD

<400>  19
atggagcgga tcagcagcct gatccacctg agcctgttct gggccggagt gatgagcgcc     60

atcgagctgg tgcccgagca ccagaccgtg cccgtgagca tcggcgtgcc cgccaccctg    120

cggtgcagca tgaagggcga ggccatcggc aactactaca tcaactggta cagaaagacc    180

cagggcaaca ccatgacctt catctaccgg gagaaggaca tctacggccc tggcttcaag    240

gacaacttcc agggcgacat cgacatcgcc aagaacctgg ccgtgctgaa gatcctggcc    300

cccagcgaga gggacgaggg cagctactac tgcgcctgcg acaccctggg catgggcggc    360

gagtacaccg acaagctgat cttcggcaag ggcacccggg tgaccgtgga gcccagaagc    420

cagccccaca ccaagcccag cgtgttcgtg atgaagaacg gcaccaacgt ggcctgcctg    480

gtgaaagagt tctaccccaa ggacatccgg atcaacctgg tgtccagcaa gaagatcacc    540

gagttcgacc ccgccatcgt gatcagcccc agcggcaagt acaacgccgt gaagctgggc    600

aagtacgagg acagcaacag cgtgacctgc agcgtgcagc acgacaacaa gaccgtgcac    660

agcaccgact tcgaggtgaa aaccgactcc accgaccacg tgaagcccaa agagaccgag    720

aacaccaagc agcccagcaa gagctgccac aagcccaagg ccatcgtgca caccgagaag    780

gtgaacatga tgagcctgac cgtgctgggc ctgcggatgc tgttcgccaa gacagtggcc    840

gtgaacttcc tgctgaccgc caagctgttc ttcctgtga                           879


<210>  20
<211>  292
<212>  PRT
<213>  ˹

<220>
<223>  hTRD

<400>  20
Met Glu Arg Ile Ser Ser Leu Ile His Leu Ser Leu Phe Trp Ala Gly 
                5                   10                  15

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

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

Ile Gly Asn Tyr Tyr Ile Asn Trp Tyr Arg Lys Thr Gln Gly Asn Thr
    50                  55                  60

Met Thr Phe Ile Tyr Arg Glu Lys Asp Ile Tyr Gly Pro Gly Phe Lys
65                  70                  75                  80

Asp Asn Phe Gln Gly Asp Ile Asp Ile Ala Lys Asn Leu Ala Val Leu
                85                  90                  95

Lys Ile Leu Ala Pro Ser Glu Arg Asp Glu Gly Ser Tyr Tyr Cys Ala
            100                 105                 110

Cys Asp Thr Leu Gly Met Gly Gly Glu Tyr Thr Asp Lys Leu Ile Phe
        115                 120                 125

Gly Lys Gly Thr Arg Val Thr Val Glu Pro Arg Ser Gln Pro His Thr
    130                 135                 140

Lys Pro Ser Val Phe Val Met Lys Asn Gly Thr Asn Val Ala Cys Leu
145                 150                 155                 160

Val Lys Glu Phe Tyr Pro Lys Asp Ile Arg Ile Asn Leu Val Ser Ser
                165                 170                 175

Lys Lys Ile Thr Glu Phe Asp Pro Ala Ile Val Ile Ser Pro Ser Gly
            180                 185                 190

Lys Tyr Asn Ala Val Lys Leu Gly Lys Tyr Glu Asp Ser Asn Ser Val
        195                 200                 205
 
Thr Cys Ser Val Gln His Asp Asn Lys Thr Val His Ser Thr Asp Phe
    210                 215                 220

Glu Val Lys Thr Asp Ser Thr Asp His Val Lys Pro Lys Glu Thr Glu
225                 230                 235                 240

Asn Thr Lys Gln Pro Ser Lys Ser Cys His Lys Pro Lys Ala Ile Val
                245                 250                 255

His Thr Glu Lys Val Asn Met Met Ser Leu Thr Val Leu Gly Leu Arg
            260                 265                 270

Met Leu Phe Ala Lys Thr Val Ala Val Asn Phe Leu Leu Thr Ala Lys
        275                 280                 285

Leu Phe Phe Leu
    290


<210>  21
<211>  45
<212>  DNA
<213>  ˹

<220>
<223>  (G4S)3

<400>  21
ggtggcggtg gctcgggcgg tggtgggtcg ggtggcggcg gatct                     45


<210>  22
<211>  15
<212>  PRT
<213>  ˹

<220>
<223>  (G4S)3

<400>  22
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
                5                   10                  15

<210>  23
<211>  135
<212>  DNA
<213>  ˹

<220>
<223>  CD8

<400>  23
accacgacgc cagcgccgcg accaccaaca ccggcgccca ccatcgcgtc gcagcccctg     60

tccctgcgcc cagaggcgtg ccggccagcg gcggggggcg cagtgcacac gagggggctg    120

gacttcgcct gtgat                                                     135


<210>  24
<211>  45
<212>  PRT
<213>  ˹

<220>
<223>  CD8

<400>  24
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>  25
<211>  39
<212>  DNA
<213>  ˹

<220>
<223>  IgG4

<400>  25
gaatcaaaat atggtcctcc ttgcccgcca tgtccggat                            45    


<210>  26
<211>  13
<212>  PRT
<213>  ˹

<220>
<223>  IgG4

<400>  26
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Asp
                5                   10


<210>  27
<211>  4242
<212>  DNA
<213>  ˹

<220>
<223>  Cas9

<400>  27
atggcgtatc cttatgacgt gcctgactat gccagcctga tggccccaaa gaagaagcgg     60 

aaggtcggta tccacggagt cccagcagcc gacaagaagt acagcatcgg cctggacatc    120

ggcaccaact ctgtgggctg ggccgtgatc accgacgagt acaaggtgcc cagcaagaaa    180

ttcaaggtgc tgggcaacac cgaccggcac agcatcaaga agaacctgat cggagccctg    240

ctgttcgaca gcggcgaaac agccgaggcc acccggctga agagaaccgc cagaagaaga    300

tacaccagac ggaagaaccg gatctgctat ctgcaagaga tcttcagcaa cgagatggcc    360

aaggtggacg acagcttctt ccacagactg gaagagtcct tcctggtgga agaggataag    420

aagcacgagc ggcaccccat cttcggcaac atcgtggacg aggtggccta ccacgagaag    480

taccccacca tctaccacct gagaaagaaa ctggtggaca gcaccgacaa ggccgacctg    540

cggctgatct atctggccct ggcccacatg atcaagttcc ggggccactt cctgatcgag    600

ggcgacctga accccgacaa cagcgacgtg gacaagctgt tcatccagct ggtgcagacc    660

tacaaccagc tgttcgagga aaaccccatc aacgccagcg gcgtggacgc caaggccatc    720

ctgtctgcca gactgagcaa gagcagacgg ctggaaaatc tgatcgccca gctgcccggc    780

gagaagaaga atggcctgtt cggaaacctg attgccctga gcctgggcct gacccccaac    840

ttcaagagca acttcgacct ggccgaggat gccaaactgc agctgagcaa ggacacctac    900

gacgacgacc tggacaacct gctggcccag atcggcgacc agtacgccga cctgtttctg    960

gccgccaaga acctgtccga cgccatcctg ctgagcgaca tcctgagagt gaacaccgag   1020

atcaccaagg cccccctgag cgcctctatg atcaagagat acgacgagca ccaccaggac   1080

ctgaccctgc tgaaagctct cgtgcggcag cagctgcctg agaagtacaa agagattttc   1140

ttcgaccaga gcaagaacgg ctacgccggc tacattgacg gcggagccag ccaggaagag   1200

ttctacaagt tcatcaagcc catcctggaa aagatggacg gcaccgagga actgctcgtg   1260

aagctgaaca gagaggacct gctgcggaag cagcggacct tcgacaacgg cagcatcccc   1320

caccagatcc acctgggaga gctgcacgcc attctgcggc ggcaggaaga tttttaccca   1380

ttcctgaagg acaaccggga aaagatcgag aagatcctga ccttccgcat cccctactac   1440

gtgggccctc tggccagggg aaacagcaga ttcgcctgga tgaccagaaa gagcgaggaa   1500

accatcaccc cctggaactt cgaggaagtg gtggacaagg gcgcttccgc ccagagcttc   1560

atcgagcgga tgaccaactt cgataagaac ctgcccaacg agaaggtgct gcccaagcac   1620

agcctgctgt acgagtactt caccgtgtat aacgagctga ccaaagtgaa atacgtgacc   1680

gagggaatga gaaagcccgc cttcctgagc ggcgagcaga aaaaggccat cgtggacctg   1740

ctgttcaaga ccaaccggaa agtgaccgtg aagcagctga aagaggacta cttcaagaaa   1800

atcgagtgct tcgactccgt ggaaatctcc ggcgtggaag atcggttcaa cgcctccctg   1860

ggcacatacc acgatctgct gaaaattatc aaggacaagg acttcctgga caatgaggaa   1920

aacgaggaca ttctggaaga tatcgtgctg accctgacac tgtttgagga cagagagatg   1980

atcgaggaac ggctgaaaac ctatgcccac ctgttcgacg acaaagtgat gaagcagctg   2040

aagcggcgga gatacaccgg ctggggcagg ctgagccgga agctgatcaa cggcatccgg   2100

gacaagcagt ccggcaagac aatcctggat ttcctgaagt ccgacggctt cgccaacaga   2160

aacttcatgc agctgatcca cgacgacagc ctgaccttta aagaggacat ccagaaagcc   2220

caggtgtccg gccagggcga tagcctgcac gagcacattg ccaatctggc cggcagcccc   2280

gccattaaga agggcatcct gcagacagtg aaggtggtgg acgagctcgt gaaagtgatg   2340

ggccggcaca agcccgagaa catcgtgatc gaaatggcca gagagaacca gaccacccag   2400

aagggacaga agaacagccg cgagagaatg aagcggatcg aagagggcat caaagagctg   2460

ggcagccaga tcctgaaaga acaccccgtg gaaaacaccc agctgcagaa cgagaagctg   2520

tacctgtact acctgcagaa tgggcgggat atgtacgtgg accaggaact ggacatcaac   2580

cggctgtccg actacgatgt ggaccatatc gtgcctcaga gctttctgaa ggacgactcc   2640

atcgacaaca aggtgctgac cagaagcgac aagaaccggg gcaagagcga caacgtgccc   2700

tccgaagagg tcgtgaagaa gatgaagaac tactggcggc agctgctgaa cgccaagctg   2760

attacccaga gaaagttcga caatctgacc aaggccgaga gaggcggcct gagcgaactg   2820

gataaggccg gcttcatcaa gagacagctg gtggaaaccc ggcagatcac aaagcacgtg   2880

gcacagatcc tggactcccg gatgaacact aagtacgacg agaatgacaa gctgatccgg   2940

gaagtgaaag tgatcaccct gaagtccaag ctggtgtccg atttccggaa ggatttccag   3000

ttttacaaag tgcgcgagat caacaactac caccacgccc acgacgccta cctgaacgcc   3060

gtcgtgggaa ccgccctgat caaaaagtac cctaagctgg aaagcgagtt cgtgtacggc   3120

gactacaagg tgtacgacgt gcggaagatg atcgccaaga gcgagcagga aatcggcaag   3180

gctaccgcca agtacttctt ctacagcaac atcatgaact ttttcaagac cgagattacc   3240

ctggccaacg gcgagatccg gaagcggcct ctgatcgaga caaacggcga aaccggggag   3300

atcgtgtggg ataagggccg ggattttgcc accgtgcgga aagtgctgag catgccccaa   3360

gtgaatatcg tgaaaaagac cgaggtgcag acaggcggct tcagcaaaga gtctatcctg   3420

cccaagagga acagcgataa gctgatcgcc agaaagaagg actgggaccc taagaagtac   3480

ggcggcttcg acagccccac cgtggcctat tctgtgctgg tggtggccaa agtggaaaag   3540

ggcaagtcca agaaactgaa gagtgtgaaa gagctgctgg ggatcaccat catggaaaga   3600

agcagcttcg agaagaatcc catcgacttt ctggaagcca agggctacaa agaagtgaaa   3660

aaggacctga tcatcaagct gcctaagtac tccctgttcg agctggaaaa cggccggaag   3720

agaatgctgg cctctgccgg cgaactgcag aagggaaacg aactggccct gccctccaaa   3780

tatgtgaact tcctgtacct ggccagccac tatgagaagc tgaagggctc ccccgaggat   3840

aatgagcaga aacagctgtt tgtggaacag cacaagcact acctggacga gatcatcgag   3900

cagatcagcg agttctccaa gagagtgatc ctggccgacg ctaatctgga caaagtgctg   3960

tccgcctaca acaagcaccg ggataagccc atcagagagc aggccgagaa tatcatccac   4020

ctgtttaccc tgaccaatct gggagcccct gccgccttca agtactttga caccaccatc   4080

gaccggaaga ggtacaccag caccaaagag gtgctggacg ccaccctgat ccaccagagc   4140

atcaccggcc tgtacgagac acggatcgac ctgtctcagc tgggaggcga caaaaggccg   4200

gcggccacga aaaaggccgg ccaggcaaaa aagaaaaagt aa                      4242


<210>  28
<211>  1413
<212>  PRT
<213>  ˹

<220>
<223>  Cas9

<400>  28
Met Ala Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Ser Leu Met Ala Pro
                5                   10                  15
 
Lys Lys Lys Arg Lys Val Gly Ile His Gly Val Pro Ala Ala Asp Lys
            20                  25                  30

Lys Tyr Ser Ile Gly Leu Asp Ile Gly Thr Asn Ser Val Gly Trp Ala
        35                  40                  45

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

Gly Asn Thr Asp Arg His Ser Ile Lys Lys Asn Leu Ile Gly Ala Leu
65                  70                  75                  80

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

Ala Arg Arg Arg Tyr Thr Arg Arg Lys Asn Arg Ile Cys Tyr Leu Gln
            100                 105                 110

Glu Ile Phe Ser Asn Glu Met Ala Lys Val Asp Asp Ser Phe Phe His
        115                 120                 125

Arg Leu Glu Glu Ser Phe Leu Val Glu Glu Asp Lys Lys His Glu Arg
    130                 135                 140 

His Pro Ile Phe Gly Asn Ile Val Asp Glu Val Ala Tyr His Glu Lys
145                 150                 155                 160

Tyr Pro Thr Ile Tyr His Leu Arg Lys Lys Leu Val Asp Ser Thr Asp
                165                 170                 175

Lys Ala Asp Leu Arg Leu Ile Tyr Leu Ala Leu Ala His Met Ile Lys
            180                 185                 190

Phe Arg Gly His Phe Leu Ile Glu Gly Asp Leu Asn Pro Asp Asn Ser
        195                 200                 205

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

Phe Glu Glu Asn Pro Ile Asn Ala Ser Gly Val Asp Ala Lys Ala Ile
225                 230                 235                 240

Leu Ser Ala Arg Leu Ser Lys Ser Arg Arg Leu Glu Asn Leu Ile Ala
                245                 250                 255

Gln Leu Pro Gly Glu Lys Lys Asn Gly Leu Phe Gly Asn Leu Ile Ala
            260                 265                 270
 
Leu Ser Leu Gly Leu Thr Pro Asn Phe Lys Ser Asn Phe Asp Leu Ala
        275                 280                 285

Glu Asp Ala Lys Leu Gln Leu Ser Lys Asp Thr Tyr Asp Asp Asp Leu
    290                 295                 300

Asp Asn Leu Leu Ala Gln Ile Gly Asp Gln Tyr Ala Asp Leu Phe Leu
305                 310                 315                 320

Ala Ala Lys Asn Leu Ser Asp Ala Ile Leu Leu Ser Asp Ile Leu Arg 
                325                 330                 335

Val Asn Thr Glu Ile Thr Lys Ala Pro Leu Ser Ala Ser Met Ile Lys
            340                 345                 350

Arg Tyr Asp Glu His His Gln Asp Leu Thr Leu Leu Lys Ala Leu Val
        355                 360                 365

Arg Gln Gln Leu Pro Glu Lys Tyr Lys Glu Ile Phe Phe Asp Gln Ser
    370                 375                 380

Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Gly Ala Ser Gln Glu Glu
385                 390                 395                 400

Phe Tyr Lys Phe Ile Lys Pro Ile Leu Glu Lys Met Asp Gly Thr Glu
                405                 410                 415

Glu Leu Leu Val Lys Leu Asn Arg Glu Asp Leu Leu Arg Lys Gln Arg
            420                 425                 430

Thr Phe Asp Asn Gly Ser Ile Pro His Gln Ile His Leu Gly Glu Leu
        435                 440                 445

His Ala Ile Leu Arg Arg Gln Glu Asp Phe Tyr Pro Phe Leu Lys Asp
    450                 455                 460

Asn Arg Glu Lys Ile Glu Lys Ile Leu Thr Phe Arg Ile Pro Tyr Tyr
465                 470                 475                 480

Val Gly Pro Leu Ala Arg Gly Asn Ser Arg Phe Ala Trp Met Thr Arg
                485                 490                 495

Lys Ser Glu Glu Thr Ile Thr Pro Trp Asn Phe Glu Glu Val Val Asp
            500                 505                 510

Lys Gly Ala Ser Ala Gln Ser Phe Ile Glu Arg Met Thr Asn Phe Asp
        515                 520                 525

Lys Asn Leu Pro Asn Glu Lys Val Leu Pro Lys His Ser Leu Leu Tyr
    530                 535                 540

Glu Tyr Phe Thr Val Tyr Asn Glu Leu Thr Lys Val Lys Tyr Val Thr
545                 550                 555                 560

Glu Gly Met Arg Lys Pro Ala Phe Leu Ser Gly Glu Gln Lys Lys Ala
                565                 570                 575

Ile Val Asp Leu Leu Phe Lys Thr Asn Arg Lys Val Thr Val Lys Gln
            580                 585                 590

Leu Lys Glu Asp Tyr Phe Lys Lys Ile Glu Cys Phe Asp Ser Val Glu
        595                 600                 605

Ile Ser Gly Val Glu Asp Arg Phe Asn Ala Ser Leu Gly Thr Tyr His
    610                 615                 620

Asp Leu Leu Lys Ile Ile Lys Asp Lys Asp Phe Leu Asp Asn Glu Glu
625                 630                 635                 640

Asn Glu Asp Ile Leu Glu Asp Ile Val Leu Thr Leu Thr Leu Phe Glu
                645                 650                 655

Asp Arg Glu Met Ile Glu Glu Arg Leu Lys Thr Tyr Ala His Leu Phe
            660                 665                 670

Asp Asp Lys Val Met Lys Gln Leu Lys Arg Arg Arg Tyr Thr Gly Trp
        675                 680                 685

Gly Arg Leu Ser Arg Lys Leu Ile Asn Gly Ile Arg Asp Lys Gln Ser
    690                 695                 700

Gly Lys Thr Ile Leu Asp Phe Leu Lys Ser Asp Gly Phe Ala Asn Arg
705                 710                 715                 720

Asn Phe Met Gln Leu Ile His Asp Asp Ser Leu Thr Phe Lys Glu Asp
                725                 730                 735

Ile Gln Lys Ala Gln Val Ser Gly Gln Gly Asp Ser Leu His Glu His
            740                 745                 750

Ile Ala Asn Leu Ala Gly Ser Pro Ala Ile Lys Lys Gly Ile Leu Gln
        755                 760                 765

Thr Val Lys Val Val Asp Glu Leu Val Lys Val Met Gly Arg His Lys 
    770                 775                 780

Pro Glu Asn Ile Val Ile Glu Met Ala Arg Glu Asn Gln Thr Thr Gln
785                 790                 795                 800

Lys Gly Gln Lys Asn Ser Arg Glu Arg Met Lys Arg Ile Glu Glu Gly
                805                 810                 815

Ile Lys Glu Leu Gly Ser Gln Ile Leu Lys Glu His Pro Val Glu Asn
            820                 825                 830

Thr Gln Leu Gln Asn Glu Lys Leu Tyr Leu Tyr Tyr Leu Gln Asn Gly
        835                 840                 845

Arg Asp Met Tyr Val Asp Gln Glu Leu Asp Ile Asn Arg Leu Ser Asp
    850                 855                 860

Tyr Asp Val Asp His Ile Val Pro Gln Ser Phe Leu Lys Asp Asp Ser
865                 870                 875                 880

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

Asp Asn Val Pro Ser Glu Glu Val Val Lys Lys Met Lys Asn Tyr Trp
            900                 905                 910

Arg Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys Phe Asp Asn
        915                 920                 925

Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp Lys Ala Gly
    930                 935                 940

Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr Lys His Val
945                 950                 955                 960

Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp Glu Asn Asp
                965                 970                 975

Lys Leu Ile Arg Glu Val Lys Val Ile Thr Leu Lys Ser Lys Leu Val
            980                 985                 990

Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys Val Arg Glu Ile Asn
        995                 1000                1005

Asn Tyr His His Ala His Asp Ala Tyr Leu Asn Ala Val Val Gly Thr
    1010                1015                1020

Ala Leu Ile Lys Lys Tyr Pro Lys Leu Glu Ser Glu Phe Val Tyr Gly
1025                1030                1035                1040

Asp Tyr Lys Val Tyr Asp Val Arg Lys Met Ile Ala Lys Ser Glu Gln
                1045                1050                1055

Glu Ile Gly Lys Ala Thr Ala Lys Tyr Phe Phe Tyr Ser Asn Ile Met
            1060                1065                1070

Asn Phe Phe Lys Thr Glu Ile Thr Leu Ala Asn Gly Glu Ile Arg Lys
        1075                1080                1085

Arg Pro Leu Ile Glu Thr Asn Gly Glu Thr Gly Glu Ile Val Trp Asp
    1090                1095                1100

Lys Gly Arg Asp Phe Ala Thr Val Arg Lys Val Leu Ser Met Pro Gln
1105                1110                1115                1120

Val Asn Ile Val Lys Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys
                1125                1130                1135

Glu Ser Ile Leu Pro Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys
            1140                1145                1150

Lys Asp Trp Asp Pro Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val
        1155                1160                1165

Ala Tyr Ser Val Leu Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys
    1170                1175                1180

Lys Leu Lys Ser Val Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg
1185                1190                1195                1200

Ser Ser Phe Glu Lys Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr 
                1205                1210                1215

Lys Glu Val Lys Lys Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu
            1220                1225                1230

Phe Glu Leu Glu Asn Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu
        1235                1240                1245

Leu Gln Lys Gly Asn Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe
    1250                1255                1260

Leu Tyr Leu Ala Ser His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp
1265                1270                1275                1280

Asn Glu Gln Lys Gln Leu Phe Val Glu Gln His Lys His Tyr Leu Asp
                1285                1290                1295

Glu Ile Ile Glu Gln Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala
            1300                1305                1310

Asp Ala Asn Leu Asp Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp 
        1315                1320                1325

Lys Pro Ile Arg Glu Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu
    1330                1335                1340

Thr Asn Leu Gly Ala Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile
1345                1350                1355                1360

Asp Arg Lys Arg Tyr Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu
                1365                1370                1375

Ile His Gln Ser Ile Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser
            1380                1385                1390

Gln Leu Gly Gly Asp Lys Arg Pro Ala Ala Thr Lys Lys Ala Gly Gln
        1395                1400                1405

Ala Lys Lys Lys Lys
    1410


<210>  29
<211>  1395
<212>  DNA
<213>  ˹

<220>
<223>  scFv-CAR

<400>  29
atccagatga cacagactac atcctccctg tctgcctctc tgggagacag agtcaccatc     60

agttgcaggg caagtcagga cattagtaaa tatttaaatt ggtatcagca gaaaccagat    120

ggaactgtta aactcctgat ctaccataca tcaagattac actcaggagt cccatcaagg    180

ttcagtggca gtgggtctgg aacagattat tctctcacca ttagcaacct ggagcaagaa    240

gatattgcca cttacttttg ccaacagggt aatacgcttc cgtacacgtt cggagggggg    300

actaagttgg aaataacagg tggcggtggc tcgggcggtg gtgggtcggg tggcggcgga    360

tctgaggtga aactgcagga gtcaggacct ggcctggtgg cgccctcaca gagcctgtcc    420

gtcacatgca ctgtctcagg ggtctcatta cccgactatg gtgtaagctg gattcgccag    480

cctccacgaa agggtctgga gtggctggga gtaatatggg gtagtgaaac cacatactat    540

aattcagctc tcaaatccag actgaccatc atcaaggaca actccaagag ccaagttttc    600

ttaaaaatga acagtctgca aactgatgac acagccattt actactgtgc caaacattat    660

tactacggtg gtagctatgc tatggactac tggggtcaag gaacctcagt caccgtctcc    720

tcaaccacga cgccagcgcc gcgaccacca acaccggcgc ccaccatcgc gtcgcagccc    780

ctgtccctgc gcccagaggc gtgccggcca gcggcggggg gcgcagtgca cacgaggggg    840

ctggacttcg cctgtgatat ctacatctgg gcgcccttgg ccgggacttg tggggtcctt    900

ctcctgtcac tggttatcac cctttactgc aaacggggca gaaagaaact cctgtatata    960

ttcaaacaac catttatgag accagtacaa actactcaag aggaagatgg ctgtagctgc   1020

cgatttccag aagaagaaga aggaggatgt gaactgagag tgaagttcag caggagcgca   1080

gacgcccccg cgtacaagca gggccagaac cagctctata acgagctcaa tctaggacga   1140

agagaggagt acgatgtttt ggacaagaga cgtggccggg accctgagat ggggggaaag   1200

ccgagaagga agaaccctca ggaaggcctg tacaatgaac tgcagaaaga taagatggcg   1260

gaggcctaca gtgagattgg gatgaaaggc gagcgccgga ggggcaaggg gcacgatggc   1320

ctttaccagg gtctcagtac agccaccaag gacacctacg acgcccttca catgcaggcc   1380

ctgccccctc gctaa                                                    1395


<210>  30
<211>  486
<212>  PRT
<213>  ˹

<220>
<223>  scFv-CAR

<400>  30
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 Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr 
                245                 250                 255

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

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

Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser 
    290                 295                 300

Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr 
305                 310                 315                 320

Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu 
                325                 330                 335

Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu 
            340                 345                 350

Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln 
        355                 360                 365

Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu
    370                 375                 380

Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly 
385                 390                 395                 400

Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln 
                405                 410                 415

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu 
            420                 425                 430

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr 
        435                 440                 445

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro 
    450                 455                 460
Arg
465
              
<210>  31
<211>  513
<212>  DNA
<213>  ˹

<220>
<223>  mTRGC

<400>  31
aaaagactcg atgcggacat ctcaccaaaa cccactatct ttctgccgtc cgtcgcggag     60

accaatcttc ataagactgg gacttacctt tgcctgttgg aaaagttctt tccagatgtg    120

attcgagttt actggaagga gaaggatggg aatacgatat tggactccca ggaaggagac    180

actttgaaga cgaatgacac ctacatgaaa ttttcatggt tgacggtgcc cgaaagagcg    240

atgggaaagg aacataggtg catagttaag cacgagaaca acaagggtgg ggcagatcaa    300

gagatttttt ttccaagcat taagaaagtg gccgtttcta ctaaacctac aacttgttgg    360

caagacaaaa acgatgtttt gcagctgcaa tttacaataa catctgcgta ctacacctat    420

cttctgcttt tgctgaagtc agttatatat ttggcgataa tctctttcag tctcctgaga    480

cgcacaagtg tgtgcgggaa tgagaagaaa agc                                 513


<210>  32
<211>  171
<212>  PRT
<213>  ˹

<220>
<223>  mTRGC

<400>  32
Lys Arg Leu Asp Ala Asp Ile Ser Pro Lys Pro Thr Ile Phe Leu Pro
                5                   10                  15

Ser Val Ala Glu Thr Asn Leu His Lys Thr Gly Thr Tyr Leu Cys Leu 
            20                  25                  30

Leu Glu Lys Phe Phe Pro Asp Val Ile Arg Val Tyr Trp Lys Glu Lys
        35                  40                  45

Asp Gly Asn Thr Ile Leu Asp Ser Gln Glu Gly Asp Thr Leu Lys Thr
    50                  55                  60

Asn Asp Thr Tyr Met Lys Phe Ser Trp Leu Thr Val Pro Glu Arg Ala
65                  70                  75                  80

Met Gly Lys Glu His Arg Cys Ile Val Lys His Glu Asn Asn Lys Gly 
                85                  90                  95

Gly Ala Asp Gln Glu Ile Phe Phe Pro Ser Ile Lys Lys Val Ala Val
            100                 105                 110

Ser Thr Lys Pro Thr Thr Cys Trp Gln Asp Lys Asn Asp Val Leu Gln
        115                 120                 125

Leu Gln Phe Thr Ile Thr Ser Ala Tyr Tyr Thr Tyr Leu Leu Leu Leu
    130                 135                 140

Leu Lys Ser Val Ile Tyr Leu Ala Ile Ile Ser Phe Ser Leu Leu Arg
145                 150                 155                 160

Arg Thr Ser Val Cys Gly Asn Glu Lys Lys Ser
                165                 170

<210>  33
<211>  456
<212>  DNA
<213>  ˹

<220>
<223>  mTRDC

<400>  33
agccaacctc cggccaagcc cagtgtattt attatgaaga acggtacgaa cgttgcgtgc     60

cttgtcaaag atttctatcc caaagaagtg accatatcct tgcgaagtag caaaaagatt    120

gttgagtttg atccagcaat tgtcatatca cctagcggga aatacagcgc cgtcaaactc    180

ggccagtacg gtgatagtaa ttctgtgacc tgttctgttc agcataattc agagacagtc    240

cactcaacgg actttgagcc gtatgctaat tcatttaaca atgagaagct gccggaacca    300

gaaaatgaca cgcaaatatc tgagccctgt tacggcccca gagtgactgt ccacaccgaa    360

aaagtcaaca tgatgtccct cacggtgctg ggacttcggt tgttgttcgc taaaaccata    420

gcaataaact tcttgctcac agtgaaactt ttcttt                              456


<210>  34
<211>  152
<212>  PRT
<213>  ˹

<220>
<223>  mTRDC

<400>  34
Ser Gln Pro Pro Ala Lys Pro Ser Val Phe Ile Met Lys Asn Gly Thr
                5                   10                  15
 
Asn Val Ala Cys Leu Val Lys Asp Phe Tyr Pro Lys Glu Val Thr Ile
            20                  25                  30

Ser Leu Arg Ser Ser Lys Lys Ile Val Glu Phe Asp Pro Ala Ile Val
        35                  40                  45
               
Ile Ser Pro Ser Gly Lys Tyr Ser Ala Val Lys Leu Gly Gln Tyr Gly 
    50                  55                  60

Asp Ser Asn Ser Val Thr Cys Ser Val Gln His Asn Ser Glu Thr Val
65                  70                  75                  80

His Ser Thr Asp Phe Glu Pro Tyr Ala Asn Ser Phe Asn Asn Glu Lys
                85                  90                  95

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

Pro Arg Val Thr Val His Thr Glu Lys Val Asn Met Met Ser Leu Thr
        115                 120                 125

Val Leu Gly Leu Arg Leu Leu Phe Ala Lys Thr Ile Ala Ile Asn Phe
    130                 135                 140

Leu Leu Thr Val Lys Leu Phe Phe
145                 150


<210>  35
<211>  60
<212>  DNA
<213>  ˹

<220>
<223>  B2mź

<400>  35
atgtcccgct ctgttgcttt ggctgtgctg gcccttttgt cccttagcgg actggaggcc     60


<210>  36
<211>  20
<212>  PRT
<213>  ˹

<220>
<223>  B2mź

<400>  36
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>  37
<211>  63
<212>  DNA
<213>  ˹

<220>
<223>  CD8ź

<400>  37
atggccttac cagtgaccgc cttgctcctg ccgctggcct tgctgctcca cgccgccagg     60

ccg                                                                   63


<210>  38
<211>  21
<212>  PRT
<213>  ˹

<220>
<223>  CD8ź

<400>  38
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>  39
<211>  66
<212>  DNA
<213>  ˹

<220>
<223>  F2A

<400>  39
gtgaaacaga ctttgaattt tgaccttctc aagttggcgg gagacgtgga gtccaaccca     60

gggccg                                                                66


<210>  40
<211>  22
<212>  PRT
<213>  ˹

<220>
<223>  F2A

<400>  40
Val Lys Gln Thr Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val
                5                   10                  15

Glu Ser Asn Pro Gly Pro
            20

