                         SEQUENCE LISTING

<110>  Julius-Maximilians-Universitt Wrzburg
 
<120>  Control and modulation of the function of gene-modified chimeric 
       antigen receptor T cells with dasatinib and other tyrosine kinase
        inhibitors

<130>  210500

<150>  EP 17205922.2
<151>  2017-12-07

<160>  51    

<170>  PatentIn version 3.5

<210>  1
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GMCSF signal peptide

<400>  1

Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 
1               5                   10                  15      


Ala Phe Leu Leu Ile Pro 
            20          


<210>  2
<211>  245
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD19 heavy chain variable domain (VH)

<400>  2

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


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


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


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


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


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


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


Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Val Lys 
        115                 120                 125             


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


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


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


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


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


Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr 
    210                 215                 220                 


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


Val Thr Val Ser Ser 
                245 


<210>  3
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  IgG4 hinge domain

<400>  3

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro 
1               5                   10          


<210>  4
<211>  28
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD28 transmembrane domain

<400>  4

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


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


<210>  5
<211>  42
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  4-1BB costimulatory domain

<400>  5

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


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


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


<210>  6
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD3z signaling domain

<400>  6

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


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


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


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


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


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


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


<210>  7
<211>  24
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  T2A ribosomal skipping sequence

<400>  7

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


Val Glu Glu Asn Pro Gly Pro Arg 
            20                  


<210>  8
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GMCSF signal peptide

<400>  8

Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 
1               5                   10                  15      


Ala Phe Leu Leu Ile Pro 
            20          


<210>  9
<211>  335
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  EGFRt

<400>  9

Arg Lys Val Cys Asn Gly Ile Gly Ile Gly Glu Phe Lys Asp Ser Leu 
1               5                   10                  15      


Ser Ile Asn Ala Thr Asn Ile Lys His Phe Lys Asn Cys Thr Ser Ile 
            20                  25                  30          


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


Thr His Thr Pro Pro Leu Asp Pro Gln Glu Leu Asp Ile Leu Lys Thr 
    50                  55                  60                  


Val Lys Glu Ile Thr Gly Phe Leu Leu Ile Gln Ala Trp Pro Glu Asn 
65                  70                  75                  80  


Arg Thr Asp Leu His Ala Phe Glu Asn Leu Glu Ile Ile Arg Gly Arg 
                85                  90                  95      


Thr Lys Gln His Gly Gln Phe Ser Leu Ala Val Val Ser Leu Asn Ile 
            100                 105                 110         


Thr Ser Leu Gly Leu Arg Ser Leu Lys Glu Ile Ser Asp Gly Asp Val 
        115                 120                 125             


Ile Ile Ser Gly Asn Lys Asn Leu Cys Tyr Ala Asn Thr Ile Asn Trp 
    130                 135                 140                 


Lys Lys Leu Phe Gly Thr Ser Gly Gln Lys Thr Lys Ile Ile Ser Asn 
145                 150                 155                 160 


Arg Gly Glu Asn Ser Cys Lys Ala Thr Gly Gln Val Cys His Ala Leu 
                165                 170                 175     


Cys Ser Pro Glu Gly Cys Trp Gly Pro Glu Pro Arg Asp Cys Val Ser 
            180                 185                 190         


Cys Arg Asn Val Ser Arg Gly Arg Glu Cys Val Asp Lys Cys Asn Leu 
        195                 200                 205             


Leu Glu Gly Glu Pro Arg Glu Phe Val Glu Asn Ser Glu Cys Ile Gln 
    210                 215                 220                 


Cys His Pro Glu Cys Leu Pro Gln Ala Met Asn Ile Thr Cys Thr Gly 
225                 230                 235                 240 


Arg Gly Pro Asp Asn Cys Ile Gln Cys Ala His Tyr Ile Asp Gly Pro 
                245                 250                 255     


His Cys Val Lys Thr Cys Pro Ala Gly Val Met Gly Glu Asn Asn Thr 
            260                 265                 270         


Leu Val Trp Lys Tyr Ala Asp Ala Gly His Val Cys His Leu Cys His 
        275                 280                 285             


Pro Asn Cys Thr Tyr Gly Cys Thr Gly Pro Gly Leu Glu Gly Cys Pro 
    290                 295                 300                 


Thr Asn Gly Pro Lys Ile Pro Ser Ile Ala Thr Gly Met Val Gly Ala 
305                 310                 315                 320 


Leu Leu Leu Leu Leu Val Val Ala Leu Gly Ile Gly Leu Phe Met 
                325                 330                 335 


<210>  10
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GMCSF signal peptide

<400>  10

Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 
1               5                   10                  15      


Ala Phe Leu Leu Ile Pro 
            20          


<210>  11
<211>  243
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD19 scFv

<400>  11

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


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


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


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


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


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


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


Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Val Lys 
        115                 120                 125             


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


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


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


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


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


Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr 
    210                 215                 220                 


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


Val Thr Val 
            


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

<220>
<223>  IgG4 hinge domain

<400>  12

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro 
1               5                   10          


<210>  13
<211>  28
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD28 transmembrane domain

<400>  13

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


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


<210>  14
<211>  41
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD28 costimulatory domain

<400>  14

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


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


Pro Arg Asp Phe Ala Ala Tyr Arg Ser 
        35                  40      


<210>  15
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD3z signaling domain

<400>  15

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


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


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


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


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


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


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


<210>  16
<211>  24
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  T2A ribosomal skipping sequence

<400>  16

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


Val Glu Glu Asn Pro Gly Pro Arg 
            20                  


<210>  17
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GMCSF signal peptide

<400>  17

Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 
1               5                   10                  15      


Ala Phe Leu Leu Ile Pro 
            20          


<210>  18
<211>  335
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  EGFRt

<400>  18

Arg Lys Val Cys Asn Gly Ile Gly Ile Gly Glu Phe Lys Asp Ser Leu 
1               5                   10                  15      


Ser Ile Asn Ala Thr Asn Ile Lys His Phe Lys Asn Cys Thr Ser Ile 
            20                  25                  30          


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


Thr His Thr Pro Pro Leu Asp Pro Gln Glu Leu Asp Ile Leu Lys Thr 
    50                  55                  60                  


Val Lys Glu Ile Thr Gly Phe Leu Leu Ile Gln Ala Trp Pro Glu Asn 
65                  70                  75                  80  


Arg Thr Asp Leu His Ala Phe Glu Asn Leu Glu Ile Ile Arg Gly Arg 
                85                  90                  95      


Thr Lys Gln His Gly Gln Phe Ser Leu Ala Val Val Ser Leu Asn Ile 
            100                 105                 110         


Thr Ser Leu Gly Leu Arg Ser Leu Lys Glu Ile Ser Asp Gly Asp Val 
        115                 120                 125             


Ile Ile Ser Gly Asn Lys Asn Leu Cys Tyr Ala Asn Thr Ile Asn Trp 
    130                 135                 140                 


Lys Lys Leu Phe Gly Thr Ser Gly Gln Lys Thr Lys Ile Ile Ser Asn 
145                 150                 155                 160 


Arg Gly Glu Asn Ser Cys Lys Ala Thr Gly Gln Val Cys His Ala Leu 
                165                 170                 175     


Cys Ser Pro Glu Gly Cys Trp Gly Pro Glu Pro Arg Asp Cys Val Ser 
            180                 185                 190         


Cys Arg Asn Val Ser Arg Gly Arg Glu Cys Val Asp Lys Cys Asn Leu 
        195                 200                 205             


Leu Glu Gly Glu Pro Arg Glu Phe Val Glu Asn Ser Glu Cys Ile Gln 
    210                 215                 220                 


Cys His Pro Glu Cys Leu Pro Gln Ala Met Asn Ile Thr Cys Thr Gly 
225                 230                 235                 240 


Arg Gly Pro Asp Asn Cys Ile Gln Cys Ala His Tyr Ile Asp Gly Pro 
                245                 250                 255     


His Cys Val Lys Thr Cys Pro Ala Gly Val Met Gly Glu Asn Asn Thr 
            260                 265                 270         


Leu Val Trp Lys Tyr Ala Asp Ala Gly His Val Cys His Leu Cys His 
        275                 280                 285             


Pro Asn Cys Thr Tyr Gly Cys Thr Gly Pro Gly Leu Glu Gly Cys Pro 
    290                 295                 300                 


Thr Asn Gly Pro Lys Ile Pro Ser Ile Ala Thr Gly Met Val Gly Ala 
305                 310                 315                 320 


Leu Leu Leu Leu Leu Val Val Ala Leu Gly Ile Gly Leu Phe Met 
                325                 330                 335 


<210>  19
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GMCSF signal peptide

<400>  19

Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 
1               5                   10                  15      


Ala Phe Leu Leu Ile Pro 
            20          


<210>  20
<211>  121
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hR12 heavy chain variable domain (VH)

<400>  20

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


Ser Leu Thr Leu Ser Cys Lys Ala Ser Gly Phe Asp Phe Ser Ala Tyr 
            20                  25                  30          


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


Ala Thr Ile Tyr Pro Ser Ser Gly Lys Thr Tyr Tyr Ala Ala Ser Val 
    50                  55                  60                  


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


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


Ala Arg Asp Ser Tyr Ala Asp Asp Gly Ala Leu Phe Asn Ile Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


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

<220>
<223>  4(GS)x3 linker

<400>  21

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


<210>  22
<211>  111
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hR12 light chain variable domain (VL)

<400>  22

Gln Leu Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Leu Gly Ser 
1               5                   10                  15      


Ser Ala Lys Ile Thr Cys Thr Leu Ser Ser Ala His Lys Thr Asp Thr 
            20                  25                  30          


Ile Asp Trp Tyr Gln Gln Leu Ala Gly Gln Ala Pro Arg Tyr Leu Met 
        35                  40                  45              


Tyr Val Gln Ser Asp Gly Ser Tyr Glu Lys Arg Ser Gly Val Pro Asp 
    50                  55                  60                  


Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ile Ile Ser 
65                  70                  75                  80  


Ser Val Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Asp Tyr 
                85                  90                  95      


Ile Gly Gly Tyr Val Phe Gly Gly Gly Thr Gln Leu Thr Val Gly 
            100                 105                 110     


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

<220>
<223>  IgG4 hinge domain

<400>  23

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro 
1               5                   10          


<210>  24
<211>  28
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD28 transmembrane domain

<400>  24

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


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


<210>  25
<211>  42
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  4-1BB costimulatory domain

<400>  25

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


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


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


<210>  26
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD3z signaling domain

<400>  26

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


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


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


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


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


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


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


<210>  27
<211>  24
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  T2A ribosomal skipping sequence

<400>  27

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


Val Glu Glu Asn Pro Gly Pro Arg 
            20                  


<210>  28
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GMCSF signal peptide

<400>  28

Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 
1               5                   10                  15      


Ala Phe Leu Leu Ile Pro 
            20          


<210>  29
<211>  335
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  EGFRt

<400>  29

Arg Lys Val Cys Asn Gly Ile Gly Ile Gly Glu Phe Lys Asp Ser Leu 
1               5                   10                  15      


Ser Ile Asn Ala Thr Asn Ile Lys His Phe Lys Asn Cys Thr Ser Ile 
            20                  25                  30          


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


Thr His Thr Pro Pro Leu Asp Pro Gln Glu Leu Asp Ile Leu Lys Thr 
    50                  55                  60                  


Val Lys Glu Ile Thr Gly Phe Leu Leu Ile Gln Ala Trp Pro Glu Asn 
65                  70                  75                  80  


Arg Thr Asp Leu His Ala Phe Glu Asn Leu Glu Ile Ile Arg Gly Arg 
                85                  90                  95      


Thr Lys Gln His Gly Gln Phe Ser Leu Ala Val Val Ser Leu Asn Ile 
            100                 105                 110         


Thr Ser Leu Gly Leu Arg Ser Leu Lys Glu Ile Ser Asp Gly Asp Val 
        115                 120                 125             


Ile Ile Ser Gly Asn Lys Asn Leu Cys Tyr Ala Asn Thr Ile Asn Trp 
    130                 135                 140                 


Lys Lys Leu Phe Gly Thr Ser Gly Gln Lys Thr Lys Ile Ile Ser Asn 
145                 150                 155                 160 


Arg Gly Glu Asn Ser Cys Lys Ala Thr Gly Gln Val Cys His Ala Leu 
                165                 170                 175     


Cys Ser Pro Glu Gly Cys Trp Gly Pro Glu Pro Arg Asp Cys Val Ser 
            180                 185                 190         


Cys Arg Asn Val Ser Arg Gly Arg Glu Cys Val Asp Lys Cys Asn Leu 
        195                 200                 205             


Leu Glu Gly Glu Pro Arg Glu Phe Val Glu Asn Ser Glu Cys Ile Gln 
    210                 215                 220                 


Cys His Pro Glu Cys Leu Pro Gln Ala Met Asn Ile Thr Cys Thr Gly 
225                 230                 235                 240 


Arg Gly Pro Asp Asn Cys Ile Gln Cys Ala His Tyr Ile Asp Gly Pro 
                245                 250                 255     


His Cys Val Lys Thr Cys Pro Ala Gly Val Met Gly Glu Asn Asn Thr 
            260                 265                 270         


Leu Val Trp Lys Tyr Ala Asp Ala Gly His Val Cys His Leu Cys His 
        275                 280                 285             


Pro Asn Cys Thr Tyr Gly Cys Thr Gly Pro Gly Leu Glu Gly Cys Pro 
    290                 295                 300                 


Thr Asn Gly Pro Lys Ile Pro Ser Ile Ala Thr Gly Met Val Gly Ala 
305                 310                 315                 320 


Leu Leu Leu Leu Leu Val Val Ala Leu Gly Ile Gly Leu Phe Met 
                325                 330                 335 


<210>  30
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GMCSF signal peptide

<400>  30

Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 
1               5                   10                  15      


Ala Phe Leu Leu Ile Pro 
            20          


<210>  31
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  huLuc63 heavy chain variable domain (VH)

<400>  31

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Tyr 
            20                  25                  30          


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


Gly Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Pro Ser Leu 
    50                  55                  60                  


Lys Asp Lys Phe Ile Ile Ser Arg Asp Asn Ala Lys Asn Ser 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 Pro Asp Gly Asn Tyr Trp Tyr Phe Asp Val Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  32
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  4(GS)x3 linker

<400>  32

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


<210>  33
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  huLuc63 light chain variable domain (VL)

<400>  33

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


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


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


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


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Val Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Ser Tyr Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105         


<210>  34
<211>  228
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  IgG4 hinge domain

<400>  34

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Pro Val 
1               5                   10                  15      


Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
            20                  25                  30          


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
        35                  40                  45              


Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
    50                  55                  60                  


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Gln Ser Thr 
65                  70                  75                  80  


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
                85                  90                  95      


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser 
            100                 105                 110         


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
        115                 120                 125             


Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val 
    130                 135                 140                 


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


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
                165                 170                 175     


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr 
            180                 185                 190         


Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val 
        195                 200                 205             


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
    210                 215                 220                 


Ser Leu Gly Lys 
225             


<210>  35
<211>  28
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD28 transmembrane domain

<400>  35

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


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


<210>  36
<211>  42
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  4-1BB costimulatory domain

<400>  36

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


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


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


<210>  37
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD3z signaling domain

<400>  37

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


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


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


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


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


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


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


<210>  38
<211>  24
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  T2A ribosomal skipping sequence

<400>  38

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


Val Glu Glu Asn Pro Gly Pro Arg 
            20                  


<210>  39
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GMCSF signal peptide

<400>  39

Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 
1               5                   10                  15      


Ala Phe Leu Leu Ile Pro 
            20          


<210>  40
<211>  335
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  EGFRt

<400>  40

Arg Lys Val Cys Asn Gly Ile Gly Ile Gly Glu Phe Lys Asp Ser Leu 
1               5                   10                  15      


Ser Ile Asn Ala Thr Asn Ile Lys His Phe Lys Asn Cys Thr Ser Ile 
            20                  25                  30          


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


Thr His Thr Pro Pro Leu Asp Pro Gln Glu Leu Asp Ile Leu Lys Thr 
    50                  55                  60                  


Val Lys Glu Ile Thr Gly Phe Leu Leu Ile Gln Ala Trp Pro Glu Asn 
65                  70                  75                  80  


Arg Thr Asp Leu His Ala Phe Glu Asn Leu Glu Ile Ile Arg Gly Arg 
                85                  90                  95      


Thr Lys Gln His Gly Gln Phe Ser Leu Ala Val Val Ser Leu Asn Ile 
            100                 105                 110         


Thr Ser Leu Gly Leu Arg Ser Leu Lys Glu Ile Ser Asp Gly Asp Val 
        115                 120                 125             


Ile Ile Ser Gly Asn Lys Asn Leu Cys Tyr Ala Asn Thr Ile Asn Trp 
    130                 135                 140                 


Lys Lys Leu Phe Gly Thr Ser Gly Gln Lys Thr Lys Ile Ile Ser Asn 
145                 150                 155                 160 


Arg Gly Glu Asn Ser Cys Lys Ala Thr Gly Gln Val Cys His Ala Leu 
                165                 170                 175     


Cys Ser Pro Glu Gly Cys Trp Gly Pro Glu Pro Arg Asp Cys Val Ser 
            180                 185                 190         


Cys Arg Asn Val Ser Arg Gly Arg Glu Cys Val Asp Lys Cys Asn Leu 
        195                 200                 205             


Leu Glu Gly Glu Pro Arg Glu Phe Val Glu Asn Ser Glu Cys Ile Gln 
    210                 215                 220                 


Cys His Pro Glu Cys Leu Pro Gln Ala Met Asn Ile Thr Cys Thr Gly 
225                 230                 235                 240 


Arg Gly Pro Asp Asn Cys Ile Gln Cys Ala His Tyr Ile Asp Gly Pro 
                245                 250                 255     


His Cys Val Lys Thr Cys Pro Ala Gly Val Met Gly Glu Asn Asn Thr 
            260                 265                 270         


Leu Val Trp Lys Tyr Ala Asp Ala Gly His Val Cys His Leu Cys His 
        275                 280                 285             


Pro Asn Cys Thr Tyr Gly Cys Thr Gly Pro Gly Leu Glu Gly Cys Pro 
    290                 295                 300                 


Thr Asn Gly Pro Lys Ile Pro Ser Ile Ala Thr Gly Met Val Gly Ala 
305                 310                 315                 320 


Leu Leu Leu Leu Leu Val Val Ala Leu Gly Ile Gly Leu Phe Met 
                325                 330                 335 


<210>  41
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GMCSF signal peptide

<400>  41

Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 
1               5                   10                  15      


Ala Phe Leu Leu Ile Pro 
            20          


<210>  42
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  huLuc63 heavy chain variable domain (VH)

<400>  42

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Tyr 
            20                  25                  30          


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


Gly Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Pro Ser Leu 
    50                  55                  60                  


Lys Asp Lys Phe Ile Ile Ser Arg Asp Asn Ala Lys Asn Ser 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 Pro Asp Gly Asn Tyr Trp Tyr Phe Asp Val Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  43
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  4(GS)x3 linker

<400>  43

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


<210>  44
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  huLuc63 light chain variable domain (VL)

<400>  44

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


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


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


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


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Val Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Ser Tyr Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105         


<210>  45
<211>  228
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  IgG4 hinge domain

<400>  45

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Pro Val 
1               5                   10                  15      


Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
            20                  25                  30          


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
        35                  40                  45              


Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
    50                  55                  60                  


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Gln Ser Thr 
65                  70                  75                  80  


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
                85                  90                  95      


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser 
            100                 105                 110         


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
        115                 120                 125             


Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val 
    130                 135                 140                 


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


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
                165                 170                 175     


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr 
            180                 185                 190         


Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val 
        195                 200                 205             


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
    210                 215                 220                 


Ser Leu Gly Lys 
225             


<210>  46
<211>  28
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD28 transmembrane domain

<400>  46

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


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


<210>  47
<211>  41
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD28 costimulatory domain

<400>  47

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


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


Pro Arg Asp Phe Ala Ala Tyr Arg Ser 
        35                  40      


<210>  48
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD3z signaling domain

<400>  48

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


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


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


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


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


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


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


<210>  49
<211>  24
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  T2A ribosomal skipping sequence

<400>  49

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


Val Glu Glu Asn Pro Gly Pro Arg 
            20                  


<210>  50
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GMCSF signal peptide

<400>  50

Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 
1               5                   10                  15      


Ala Phe Leu Leu Ile Pro 
            20          


<210>  51
<211>  335
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  EGFRt

<400>  51

Arg Lys Val Cys Asn Gly Ile Gly Ile Gly Glu Phe Lys Asp Ser Leu 
1               5                   10                  15      


Ser Ile Asn Ala Thr Asn Ile Lys His Phe Lys Asn Cys Thr Ser Ile 
            20                  25                  30          


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


Thr His Thr Pro Pro Leu Asp Pro Gln Glu Leu Asp Ile Leu Lys Thr 
    50                  55                  60                  


Val Lys Glu Ile Thr Gly Phe Leu Leu Ile Gln Ala Trp Pro Glu Asn 
65                  70                  75                  80  


Arg Thr Asp Leu His Ala Phe Glu Asn Leu Glu Ile Ile Arg Gly Arg 
                85                  90                  95      


Thr Lys Gln His Gly Gln Phe Ser Leu Ala Val Val Ser Leu Asn Ile 
            100                 105                 110         


Thr Ser Leu Gly Leu Arg Ser Leu Lys Glu Ile Ser Asp Gly Asp Val 
        115                 120                 125             


Ile Ile Ser Gly Asn Lys Asn Leu Cys Tyr Ala Asn Thr Ile Asn Trp 
    130                 135                 140                 


Lys Lys Leu Phe Gly Thr Ser Gly Gln Lys Thr Lys Ile Ile Ser Asn 
145                 150                 155                 160 


Arg Gly Glu Asn Ser Cys Lys Ala Thr Gly Gln Val Cys His Ala Leu 
                165                 170                 175     


Cys Ser Pro Glu Gly Cys Trp Gly Pro Glu Pro Arg Asp Cys Val Ser 
            180                 185                 190         


Cys Arg Asn Val Ser Arg Gly Arg Glu Cys Val Asp Lys Cys Asn Leu 
        195                 200                 205             


Leu Glu Gly Glu Pro Arg Glu Phe Val Glu Asn Ser Glu Cys Ile Gln 
    210                 215                 220                 


Cys His Pro Glu Cys Leu Pro Gln Ala Met Asn Ile Thr Cys Thr Gly 
225                 230                 235                 240 


Arg Gly Pro Asp Asn Cys Ile Gln Cys Ala His Tyr Ile Asp Gly Pro 
                245                 250                 255     


His Cys Val Lys Thr Cys Pro Ala Gly Val Met Gly Glu Asn Asn Thr 
            260                 265                 270         


Leu Val Trp Lys Tyr Ala Asp Ala Gly His Val Cys His Leu Cys His 
        275                 280                 285             


Pro Asn Cys Thr Tyr Gly Cys Thr Gly Pro Gly Leu Glu Gly Cys Pro 
    290                 295                 300                 


Thr Asn Gly Pro Lys Ile Pro Ser Ile Ala Thr Gly Met Val Gly Ala 
305                 310                 315                 320 


Leu Leu Leu Leu Leu Val Val Ala Leu Gly Ile Gly Leu Phe Met 
                325                 330                 335 


