                         SEQUENCE LISTING

<110>  CUROCELL INC.
       KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGY
 
<120>  ENHANCED IMMUNE CELLS USING DUAL SHRNA AND COMPOSITION INCLUDING 
       THE SAME

<130>  14570-002-228

<140>
<141>

<150>  US 62/875,504
<151>  2019-07-17

<160>  62    

<170>  PatentIn version 3.5

<210>  1
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against TGFBR2

<400>  1
ggagaaagaa tgacgagaac a                                                 21


<210>  2
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against TGFBR2

<400>  2
gctccagaag tcctagaatc c                                                 21


<210>  3
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against TGFBR2

<400>  3
ggaggagaag attcctgaag a                                                 21


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

<220>
<223>  shRNA against TGFBR2

<400>  4
gcatagaggc gcctagaaat t                                                 21


<210>  5
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against TGFBR2

<400>  5
ggttcctgtg tgcccttatt t                                                 21


<210>  6
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against TGFBR2

<400>  6
gcgcctagaa attccacttg c                                                 21


<210>  7
<211>  19
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against TGFBR2

<400>  7
tcctgcatga gcaactgca                                                    19


<210>  8
<211>  19
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against TGFBR2

<400>  8
gcttctccaa agtgcatta                                                    19


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

<220>
<223>  shRNA against TGFBR2

<400>  9
ccacgtgtgc caacaacat                                                    19


<210>  10
<211>  19
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against TGFBR2

<400>  10
gctccaatat cctcgtgaa                                                    19


<210>  11
<211>  19
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against TGFBR2

<400>  11
cctgtgtcga aagcatgaa                                                    19


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

<220>
<223>  shRNA against TGFBR2

<400>  12
gctccctaaa cactaccaa                                                    19


<210>  13
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against PD1

<400>  13
tggaacccat tcctgaaatt a                                                 21


<210>  14
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against PD1

<400>  14
ggaacccatt cctgaaatta t                                                 21


<210>  15
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against PD1

<400>  15
gaacccattc ctgaaattat t                                                 21


<210>  16
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against PD1

<400>  16
acccattcct gaaattattt a                                                 21


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

<220>
<223>  shRNA against PD1

<400>  17
cccattcctg aaattattta a                                                 21


<210>  18
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against PD1

<400>  18
ccttccctgt ggttctatta t                                                 21


<210>  19
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against PD1

<400>  19
cttccctgtg gttctattat a                                                 21


<210>  20
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against PD1

<400>  20
ttccctgtgg ttctattata t                                                 21


<210>  21
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against PD1

<400>  21
tccctgtggt tctattatat t                                                 21


<210>  22
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against PD1

<400>  22
ccctgtggtt ctattatatt a                                                 21


<210>  23
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against PD1

<400>  23
cctgtggttc tattatatta t                                                 21


<210>  24
<211>  19
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  TGFBR2 primer Forward

<400>  24
acgtgttgag agatcgagg                                                    19


<210>  25
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  TGFBR2 primer Reverse

<400>  25
cccagcactc agtcaacgtc                                                   20


<210>  26
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PD-1 primer Forward

<400>  26
cctccacctt tacacatgcc                                                   20


<210>  27
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PD-1 primer Reverse

<400>  27
cttactgcct cagcttccct                                                   20


<210>  28
<211>  47
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Cloning primers

<400>  28
ggtatactct agacatatgg ctagcactag tcaaaaacct gtggttc                     47


<210>  29
<211>  26
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Cloning primers

<400>  29
ttgtaccgtt aacgatccga cgccgc                                            26


<210>  30
<211>  102
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Cloning primers

<400>  30
tgactagtca aaaacctgtg gttctattat attattctct tgaaataata taatagaacc       60

acaggcggtg tttcgtcctt tccacaagat atataaagcc aa                         102


<210>  31
<211>  50
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Cloning primers

<400>  31
gtaccgttaa caaggtcggg caggaagagg gcctatttcc catgattcct                  50


<210>  32
<211>  39
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Cloning primers

<400>  32
aggactagtc aaaaaggaat tcgctcagaa gaaatctct                              39


<210>  33
<211>  27
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Cloning primers

<400>  33
ctagctagcg atccgacgcc gccatct                                           27


<210>  34
<211>  42
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Cloning primers

<400>  34
atgttaacca aaaacctgtg gttctattat attattctct tg                          42


<210>  35
<211>  34
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Cloning primers

<400>  35
tcactagtaa ggtcgggcag gaagagggcc tatt                                   34


<210>  36
<211>  29
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Cloning primers

<400>  36
taggccctca ctagtgatcc gacgccgcc                                         29


<210>  37
<211>  38
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Cloning primers

<400>  37
ctagctagcc aaaaaggaat tcgctcagaa gaaatctc                               38


<210>  38
<211>  409
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shPD-1-mU6-MCS base sequence

<400>  38
gttaacgatc cgacgccgcc atctctaggc ccgcgccggc cccctcgcac agacttgtgg       60

gagaagctcg gctactcccc tgccccggtt aatttgcata taatatttcc tagtaactat      120

agaggcttaa tgtgcgataa aagacagata atctgttctt tttaatacta gctacatttt      180

acatgatagg cttggatttc tataagagat acaaatacta aattattatt ttaaaaaaca      240

gcacaaaagg aaactcaccc taactgtaaa gtaattgtgt gttttgagac tataaatatc      300

ccttggagaa aagccttgtt tgcctgtggt tctattatat tatttcaaga gaataatata      360

atagaaccac aggtttttga ctagtgctag ccatatgtct agagtatac                  409


<210>  39
<211>  328
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  hU6-shPD-1 base sequence

<400>  39
gttaacaagg tcgggcagga agagggccta tttcccatga ttccttcata tttgcatata       60

cgatacaagg ctgttagaga gataattaga attaatttga ctgtaaacac aaagatatta      120

gtacaaaata cgtgacgtag aaagtaataa tttcttgggt agtttgcagt tttaaaatta      180

tgttttaaaa tggactatca tatgcttacc gtaacttgaa agtatttcga tttcttggct      240

ttatatatct tgtggaaagg acgaaacacc gcctgtggtt ctattatatt atttcaagag      300

aataatataa tagaaccaca ggtttttg                                         328


<210>  40
<211>  468
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD22-CAR

<400>  40

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


Thr Leu Ser Leu Thr Cys Ala Ile Ser Gly Asp Ser Val Ser Ser Asn 
            20                  25                  30          


Ser Ala Ala Trp Asn Trp Ile Arg Gln Ser Pro Ser Arg Gly Leu Glu 
        35                  40                  45              


Trp Leu Gly Arg Thr Tyr Tyr Arg Ser Lys Trp Tyr Asn Asp Tyr Ala 
    50                  55                  60                  


Val Ser Val Lys Ser Arg Ile Thr Ile Asn Pro Asp Thr Ser Lys Asn 
65                  70                  75                  80  


Gln Phe Ser Leu Gln Leu Asn Ser Val Thr Pro Glu Asp Thr Ala Val 
                85                  90                  95      


Tyr Tyr Cys Ala Arg Glu Val Thr Gly Asp Leu Glu Asp Ala Phe Asp 
            100                 105                 110         


Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly 
        115                 120                 125             


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


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


Thr Cys Arg Ala Ser Gln Thr Ile Trp Ser Tyr Leu Asn Trp Tyr Gln 
                165                 170                 175     


Gln Arg Pro Gly Lys Ala Pro Asn Leu Leu Ile Tyr Ala Ala Ser Ser 
            180                 185                 190         


Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Arg Gly Ser Gly Thr 
        195                 200                 205             


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


Tyr Tyr Cys Gln Gln Ser Tyr Ser Ile Pro Gln Thr Phe Gly Gln Gly 
225                 230                 235                 240 


Thr Lys Leu Glu Ile Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro 
                245                 250                 255     


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


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


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


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


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


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


Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala 
        355                 360                 365             


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


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


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


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


Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly 
        435                 440                 445             


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


Leu Pro Pro Arg 
465             


<210>  41
<211>  486
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD19-CAR

<400>  41

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu 
1               5                   10                  15      


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


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


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


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


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


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


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


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 
    130                 135                 140                 


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


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


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


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


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


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


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


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


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


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


Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly 
305                 310                 315                 320 


Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg 
                325                 330                 335     


Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln 
            340                 345                 350         


Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu 
        355                 360                 365             


Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala 
    370                 375                 380                 


Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu 
385                 390                 395                 400 


Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp 
                405                 410                 415     


Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu 
            420                 425                 430         


Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile 
        435                 440                 445             


Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr 
    450                 455                 460                 


Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met 
465                 470                 475                 480 


Gln Ala Leu Pro Pro Arg 
                485     


<210>  42
<211>  782
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Delta LNGFR_P2A_CD19-CAR

<400>  42

Met Gly Ala Gly Ala Thr Gly Arg Ala Met Asp Gly Pro Arg Leu Leu 
1               5                   10                  15      


Leu Leu Leu Leu Leu Gly Val Ser Leu Gly Gly Ala Lys Glu Ala Cys 
            20                  25                  30          


Pro Thr Gly Leu Tyr Thr His Ser Gly Glu Cys Cys Lys Ala Cys Asn 
        35                  40                  45              


Leu Gly Glu Gly Val Ala Gln Pro Cys Gly Ala Asn Gln Thr Val Cys 
    50                  55                  60                  


Glu Pro Cys Leu Asp Ser Val Thr Phe Ser Asp Val Val Ser Ala Thr 
65                  70                  75                  80  


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


Ala Pro Cys Val Glu Ala Asp Asp Ala Val Cys Arg Cys Ala Tyr Gly 
            100                 105                 110         


Tyr Tyr Gln Asp Glu Thr Thr Gly Arg Cys Glu Ala Cys Arg Val Cys 
        115                 120                 125             


Glu Ala Gly Ser Gly Leu Val Phe Ser Cys Gln Asp Lys Gln Asn Thr 
    130                 135                 140                 


Val Cys Glu Glu Cys Pro Asp Gly Thr Tyr Ser Asp Glu Ala Asn His 
145                 150                 155                 160 


Val Asp Pro Cys Leu Pro Cys Thr Val Cys Glu Asp Thr Glu Arg Gln 
                165                 170                 175     


Leu Arg Glu Cys Thr Arg Trp Ala Asp Ala Glu Cys Glu Glu Ile Pro 
            180                 185                 190         


Gly Arg Trp Ile Thr Arg Ser Thr Pro Pro Glu Gly Ser Asp Ser Thr 
        195                 200                 205             


Ala Pro Ser Thr Gln Glu Pro Glu Ala Pro Pro Glu Gln Asp Leu Ile 
    210                 215                 220                 


Ala Ser Thr Val Ala Gly Val Val Thr Thr Val Met Gly Ser Ser Gln 
225                 230                 235                 240 


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


Ser Ile Leu Ala Ala Val Val Val Gly Leu Val Ala Tyr Ile Ala Phe 
            260                 265                 270         


Lys Arg Trp Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala 
        275                 280                 285             


Gly Asp Val Glu Glu Asn Pro Gly Pro Ala Leu Pro Val Thr Ala Leu 
    290                 295                 300                 


Leu Leu Pro Leu Ala Leu Leu Leu His Ala Ala Arg Pro Asp Ile Gln 
305                 310                 315                 320 


Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly Asp Arg Val 
                325                 330                 335     


Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp 
            340                 345                 350         


Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile Tyr His Thr 
        355                 360                 365             


Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser 
    370                 375                 380                 


Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln Glu Asp Ile 
385                 390                 395                 400 


Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly 
                405                 410                 415     


Gly Gly Thr Lys Leu Glu Ile Thr Gly Gly Gly Gly Ser Gly Gly Gly 
            420                 425                 430         


Gly Ser Gly Gly Gly Gly Ser Glu Val Lys Leu Gln Glu Ser Gly Pro 
        435                 440                 445             


Gly Leu Val Ala Pro Ser Gln Ser Leu Ser Val Thr Cys Thr Val Ser 
    450                 455                 460                 


Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro 
465                 470                 475                 480 


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


Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu Thr Ile Ile Lys Asp Asn 
            500                 505                 510         


Ser Lys Ser Gln Val Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp 
        515                 520                 525             


Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr 
    530                 535                 540                 


Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Thr 
545                 550                 555                 560 


Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser 
                565                 570                 575     


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


Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp 
        595                 600                 605             


Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile 
    610                 615                 620                 


Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys 
625                 630                 635                 640 


Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys 
                645                 650                 655     


Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val 
            660                 665                 670         


Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn 
        675                 680                 685             


Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val 
    690                 695                 700                 


Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg 
705                 710                 715                 720 


Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys 
                725                 730                 735     


Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg 
            740                 745                 750         


Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys 
        755                 760                 765             


Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
    770                 775                 780         


<210>  43
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against TGFBR1

<400>  43
ggagattgtt ggtacccaag g                                                 21


<210>  44
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against TGFBR1

<400>  44
gcagctaggc ttacagcatt g                                                 21


<210>  45
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against TGFBR1

<400>  45
ggtcctttct gtgcactatg a                                                 21


<210>  46
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against TGFBR1

<400>  46
ggtggtagct aaagaacatt c                                                 21


<210>  47
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  shRNA against TGFBR1

<400>  47
ggacctgtct acaggtgatc t                                                 21


<210>  48
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  TGFBR1 primer Forward

<400>  48
acatgattca gccacagata cc                                                22


<210>  49
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  TGFBR1 primer Reverse

<400>  49
gcatagatgt cagcacgttt g                                                 21


<210>  50
<211>  396
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  mU6-TIGIT shRNA

<400>  50
tctagacata tggctagcga tccgacgccg ccatctctag gcccgcgccg gccccctcgc       60

acagacttgt gggagaagct cggctactcc cctgccccgg ttaatttgca tataatattt      120

cctagtaact atagaggctt aatgtgcgat aaaagacaga taatctgttc tttttaatac      180

tagctacatt ttacatgata ggcttggatt tctataagag atacaaatac taaattatta      240

ttttaaaaaa cagcacaaaa ggaaactcac cctaactgta aagtaattgt gtgttttgag      300

actataaata tcccttggag aaaagccttg tttgctgcat gactacttca atgtttcaag      360

agaacattga agtagtcatg cagctttttg actagt                                396


<210>  51
<211>  396
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  mU6-TGFBR2 shRNA#1

<400>  51
tctagacata tggctagcga tccgacgccg ccatctctag gcccgcgccg gccccctcgc       60

acagacttgt gggagaagct cggctactcc cctgccccgg ttaatttgca tataatattt      120

cctagtaact atagaggctt aatgtgcgat aaaagacaga taatctgttc tttttaatac      180

tagctacatt ttacatgata ggcttggatt tctataagag atacaaatac taaattatta      240

ttttaaaaaa cagcacaaaa ggaaactcac cctaactgta aagtaattgt gtgttttgag      300

actataaata tcccttggag aaaagccttg tttggagaaa gaatgacgag aacattcaag      360

agatgttctc gtcattcttt ctcctttttg actagt                                396


<210>  52
<211>  396
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  mU6-TGFBR2 shRNA#3

<400>  52
tctagacata tggctagcga tccgacgccg ccatctctag gcccgcgccg gccccctcgc       60

acagacttgt gggagaagct cggctactcc cctgccccgg ttaatttgca tataatattt      120

cctagtaact atagaggctt aatgtgcgat aaaagacaga taatctgttc tttttaatac      180

tagctacatt ttacatgata ggcttggatt tctataagag atacaaatac taaattatta      240

ttttaaaaaa cagcacaaaa ggaaactcac cctaactgta aagtaattgt gtgttttgag      300

actataaata tcccttggag aaaagccttg tttggaggag aagattcctg aagattcaag      360

agatcttcag gaatcttctc ctcctttttg actagt                                396


<210>  53
<211>  396
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  mU6-TGFBR2 shRNA#4

<400>  53
tctagacata tggctagcga tccgacgccg ccatctctag gcccgcgccg gccccctcgc       60

acagacttgt gggagaagct cggctactcc cctgccccgg ttaatttgca tataatattt      120

cctagtaact atagaggctt aatgtgcgat aaaagacaga taatctgttc tttttaatac      180

tagctacatt ttacatgata ggcttggatt tctataagag atacaaatac taaattatta      240

ttttaaaaaa cagcacaaaa ggaaactcac cctaactgta aagtaattgt gtgttttgag      300

actataaata tcccttggag aaaagccttg tttgcataga ggcgcctaga aattttcaag      360

agaaatttct aggcgcctct atgctttttg actagt                                396


<210>  54
<211>  396
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  mU6-TGFBR2 shRNA#5

<400>  54
tctagacata tggctagcga tccgacgccg ccatctctag gcccgcgccg gccccctcgc       60

acagacttgt gggagaagct cggctactcc cctgccccgg ttaatttgca tataatattt      120

cctagtaact atagaggctt aatgtgcgat aaaagacaga taatctgttc tttttaatac      180

tagctacatt ttacatgata ggcttggatt tctataagag atacaaatac taaattatta      240

ttttaaaaaa cagcacaaaa ggaaactcac cctaactgta aagtaattgt gtgttttgag      300

actataaata tcccttggag aaaagccttg tttggttcct gtgtgccctt atttttcaag      360

agaaaataag ggcacacagg aacctttttg actagt                                396


<210>  55
<211>  392
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  mU6-TGFBR2 shRNA#7

<400>  55
tctagacata tggctagcga tccgacgccg ccatctctag gcccgcgccg gccccctcgc       60

acagacttgt gggagaagct cggctactcc cctgccccgg ttaatttgca tataatattt      120

cctagtaact atagaggctt aatgtgcgat aaaagacaga taatctgttc tttttaatac      180

tagctacatt ttacatgata ggcttggatt tctataagag atacaaatac taaattatta      240

ttttaaaaaa cagcacaaaa ggaaactcac cctaactgta aagtaattgt gtgttttgag      300

actataaata tcccttggag aaaagccttg ttttcctgca tgagcaactg cattcaagag      360

atgcagttgc tcatgcagga tttttgacta gt                                    392


<210>  56
<211>  392
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  mU6-TGFBR2 shRNA#8

<400>  56
tctagacata tggctagcga tccgacgccg ccatctctag gcccgcgccg gccccctcgc       60

acagacttgt gggagaagct cggctactcc cctgccccgg ttaatttgca tataatattt      120

cctagtaact atagaggctt aatgtgcgat aaaagacaga taatctgttc tttttaatac      180

tagctacatt ttacatgata ggcttggatt tctataagag atacaaatac taaattatta      240

ttttaaaaaa cagcacaaaa ggaaactcac cctaactgta aagtaattgt gtgttttgag      300

actataaata tcccttggag aaaagccttg tttgcttctc caaagtgcat tattcaagag      360

ataatgcact ttggagaagc tttttgacta gt                                    392


<210>  57
<211>  26
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer #1

<400>  57
ggggatcccc ccatcagtcc gcaaag                                            26


<210>  58
<211>  43
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer #2

<400>  58
aagttagtag ctccgcttcc ccacctcttg aaggctatgt agg                         43


<210>  59
<211>  87
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer #3

<400>  59
ggaagcggag ctactaactt cagcctgctg aagcaggctg gcgacgtgga ggagaaccct       60

ggacctgcct taccagtgac cgccttg                                           87


<210>  60
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer #4

<400>  60
gttgattgtc gacttagcga ggg                                               23


<210>  61
<211>  495
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  EGFR-CAR

<400>  61

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu 
1               5                   10                  15      


His Ala Ala Arg Pro Asp Glu Val Gln Leu Val Glu Ser Gly Gly Gly 
            20                  25                  30          


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


Phe Ser Phe Thr Asn Tyr Gly Val His Trp Val Arg Gln Ala Pro Gly 
    50                  55                  60                  


Lys Gly Leu Glu Trp Val Ser Val Ile Trp Ser Gly Gly Asn Thr Asp 
65                  70                  75                  80  


Tyr Asn Thr Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser 
                85                  90                  95      


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


Ala Val Tyr Tyr Cys Ala Arg Ala Leu Thr Tyr Tyr Asp Tyr Glu Phe 
        115                 120                 125             


Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly 
    130                 135                 140                 


Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
145                 150                 155                 160 


Ser Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro 
                165                 170                 175     


Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Ile Gly Thr 
            180                 185                 190         


Asn Ile His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 
        195                 200                 205             


Ile Tyr Tyr Ala Ser Glu Ser Ile Ser Gly Ile Pro Ala Arg Phe Ser 
    210                 215                 220                 


Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu 
225                 230                 235                 240 


Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Asn Asn Asn Trp Pro 
                245                 250                 255     


Thr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Ser Leu Glu 
            260                 265                 270         


Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala 
        275                 280                 285             


Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly 
    290                 295                 300                 


Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile 
305                 310                 315                 320 


Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val 
                325                 330                 335     


Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe 
            340                 345                 350         


Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly 
        355                 360                 365             


Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg 
    370                 375                 380                 


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


Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp 
                405                 410                 415     


Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro 
            420                 425                 430         


Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp 
        435                 440                 445             


Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg 
    450                 455                 460                 


Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr 
465                 470                 475                 480 


Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
                485                 490                 495 


<210>  62
<211>  251
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Cetuximab scFv

<400>  62

Asp Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
1               5                   10                  15      


Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Thr Asn 
            20                  25                  30          


Tyr Gly Val His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
        35                  40                  45              


Val Ser Val Ile Trp Ser Gly Gly Asn Thr Asp Tyr Asn Thr Ser Val 
    50                  55                  60                  


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


Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Ala Leu Thr Tyr Tyr Asp Tyr Glu Phe Ala Tyr Trp Gly Gln 
            100                 105                 110         


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


Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Leu 
    130                 135                 140                 


Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr 
145                 150                 155                 160 


Leu Ser Cys Arg Ala Ser Gln Ser Ile Gly Thr Asn Ile His Trp Tyr 
                165                 170                 175     


Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Tyr Ala Ser 
            180                 185                 190         


Glu Ser Ile Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly 
        195                 200                 205             


Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp Phe Ala 
    210                 215                 220                 


Val Tyr Tyr Cys Gln Gln Asn Asn Asn Trp Pro Thr Thr Phe Gly Gln 
225                 230                 235                 240 


Gly Thr Lys Leu Glu Ile Lys Gly Ser Leu Glu 
                245                 250     


