                         SEQUENCE LISTING

<110>  Miltenyi Biotec GmbH
 
<120>  Adapter chimeric antigen receptor expressing cells for targeting 
       of multiple antigens

<130>  Mil_099

<160>  20    

<170>  PatentIn version 3.5

<210>  1
<211>  122
<212>  PRT
<213>  artificial sequence

<220>
<223>  Anti-Biotin antibody (Bio3-18E7.2.A7.A4.A4) heavy chain (VH)

<400>  1

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


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


Ala Met Ser Trp Val Arg Gln Thr Pro Glu Thr Arg Leu Asn Trp Val 
        35                  40                  45              


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


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


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


Val Arg Gln Arg Val Gly Asp Tyr Val Ser Ser Leu Leu Gly Tyr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
        115                 120         


<210>  2
<211>  112
<212>  PRT
<213>  artificial sequence

<220>
<223>  Anti-Biotin antibody (Bio3-18E7.2.A7.A4.A4) light chain (VL)

<400>  2

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


Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 
            20                  25                  30          


Asn Gly Asn Thr Tyr Leu His Trp Phe Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


Pro Asn Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 
    50                  55                  60                  


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


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


Thr His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


<210>  3
<211>  21
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CD8 Leader sequence (human)

<400>  3

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 
            20      


<210>  4
<211>  15
<212>  PRT
<213>  Artificial sequence

<220>
<223>  scFv linker sequence

<400>  4

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


<210>  5
<211>  14
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Spacer #A (human IgG4 HC hinge)

<400>  5

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


<210>  6
<211>  47
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Spacer #B (human CD8 stalk)

<400>  6

Ala Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr 
1               5                   10                  15      


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


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


<210>  7
<211>  230
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Spacer #C (human IgG4 HC hinge+CH2+CH3)

<400>  7

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


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


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


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


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


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


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


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


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


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


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


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


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


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


Ser Leu Ser Leu Gly Lys 
225                 230 


<210>  8
<211>  24
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CD8 Transmembrane (human)

<400>  8

Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu 
1               5                   10                  15      


Ser Leu Val Ile Thr Leu Tyr Cys 
            20                  


<210>  9
<211>  42
<212>  PRT
<213>  Artificial sequence

<220>
<223>  4-1BB (human)

<400>  9

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>  10
<211>  112
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CD3zeta chain (human)

<400>  10

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>  11
<211>  462
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CD8Leader-anti-BioVL/VH-IgG4Hinge-CD8TM-41BB-CD3z

<400>  11

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 Val Val Met Thr Gln Thr Pro Leu Ser Leu 
            20                  25                  30          


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


Ser Leu Val His Ser Asn Gly Asn Thr Tyr Leu His Trp Phe Leu Gln 
    50                  55                  60                  


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


Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
                85                  90                  95      


Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr 
            100                 105                 110         


Phe Cys Ser Gln Ser Thr His Val Pro Tyr Thr Phe Gly Gly Gly Thr 
        115                 120                 125             


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


Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val 
145                 150                 155                 160 


Lys Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Val Ser Gly Phe Thr 
                165                 170                 175     


Phe Ser Asn Tyr Ala Met Ser Trp Val Arg Gln Thr Pro Glu Thr Arg 
            180                 185                 190         


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


Pro Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys 
    210                 215                 220                 


Asp Thr Leu Tyr Leu Gln Met Ser Ser Leu Arg Ser Glu Asp Thr Ala 
225                 230                 235                 240 


Met Tyr Tyr Cys Val Arg Gln Arg Val Gly Asp Tyr Val Ser Ser Leu 
                245                 250                 255     


Leu Gly Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Ala Ser 
            260                 265                 270         


Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ile Tyr Ile Trp 
        275                 280                 285             


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


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


Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys 
                325                 330                 335     


Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val 
            340                 345                 350         


Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn 
        355                 360                 365             


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


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


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


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


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


Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
    450                 455                 460         


<210>  12
<211>  462
<212>  PRT
<213>  Artificial sequence

<220>
<223>   CD8Leader-anti-BioVH/VL-IgG4Hinge-CD8TM-41BB-CD3z

<400>  12

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 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu 
            20                  25                  30          


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


Thr Phe Ser Asn Tyr Ala Met Ser Trp Val Arg Gln Thr Pro Glu Thr 
    50                  55                  60                  


Arg Leu Asn Trp Val Ala Thr Ile Thr Gly Gly Gly Ser Tyr Thr Tyr 
65                  70                  75                  80  


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


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


Ala Met Tyr Tyr Cys Val Arg Gln Arg Val Gly Asp Tyr Val Ser Ser 
        115                 120                 125             


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


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Val 
145                 150                 155                 160 


Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly Asp Gln 
                165                 170                 175     


Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser Asn Gly 
            180                 185                 190         


Asn Thr Tyr Leu His Trp Phe Leu Gln Lys Pro Gly Gln Ser Pro Asn 
        195                 200                 205             


Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro Asp Arg 
    210                 215                 220                 


Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg 
225                 230                 235                 240 


Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Ser Thr His 
                245                 250                 255     


Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Ala Ser 
            260                 265                 270         


Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ile Tyr Ile Trp 
        275                 280                 285             


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


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


Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys 
                325                 330                 335     


Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val 
            340                 345                 350         


Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn 
        355                 360                 365             


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


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


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


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


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


Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
    450                 455                 460         


<210>  13
<211>  495
<212>  PRT
<213>  Artificial sequence

<220>
<223>   CD8Leader-anti-BioVL/VH-CD8Stalk-CD8TM-41BB-CD3z

<400>  13

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 Val Val Met Thr Gln Thr Pro Leu Ser Leu 
            20                  25                  30          


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


Ser Leu Val His Ser Asn Gly Asn Thr Tyr Leu His Trp Phe Leu Gln 
    50                  55                  60                  


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


Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
                85                  90                  95      


Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr 
            100                 105                 110         


Phe Cys Ser Gln Ser Thr His Val Pro Tyr Thr Phe Gly Gly Gly Thr 
        115                 120                 125             


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


Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val 
145                 150                 155                 160 


Lys Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Val Ser Gly Phe Thr 
                165                 170                 175     


Phe Ser Asn Tyr Ala Met Ser Trp Val Arg Gln Thr Pro Glu Thr Arg 
            180                 185                 190         


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


Pro Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys 
    210                 215                 220                 


Asp Thr Leu Tyr Leu Gln Met Ser Ser Leu Arg Ser Glu Asp Thr Ala 
225                 230                 235                 240 


Met Tyr Tyr Cys Val Arg Gln Arg Val Gly Asp Tyr Val Ser Ser Leu 
                245                 250                 255     


Leu Gly Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Ala Ser 
            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>  14
<211>  495
<212>  PRT
<213>  Artificial sequence

<220>
<223>   CD8Leader-anti-BioVH/VL-CD8Stalk-CD8TM-41BB-CD3z

<400>  14

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 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu 
            20                  25                  30          


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


Thr Phe Ser Asn Tyr Ala Met Ser Trp Val Arg Gln Thr Pro Glu Thr 
    50                  55                  60                  


Arg Leu Asn Trp Val Ala Thr Ile Thr Gly Gly Gly Ser Tyr Thr Tyr 
65                  70                  75                  80  


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


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


Ala Met Tyr Tyr Cys Val Arg Gln Arg Val Gly Asp Tyr Val Ser Ser 
        115                 120                 125             


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


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Val 
145                 150                 155                 160 


Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly Asp Gln 
                165                 170                 175     


Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser Asn Gly 
            180                 185                 190         


Asn Thr Tyr Leu His Trp Phe Leu Gln Lys Pro Gly Gln Ser Pro Asn 
        195                 200                 205             


Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro Asp Arg 
    210                 215                 220                 


Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg 
225                 230                 235                 240 


Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Ser Thr His 
                245                 250                 255     


Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Ala Ser 
            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>  15
<211>  678
<212>  PRT
<213>  Artificial sequence

<220>
<223>   CD8Leader-anti-BioVL/VH- IgG4Hinge+CH2+CH3-CD8TM-41BB-CD3z

<400>  15

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 Val Val Met Thr Gln Thr Pro Leu Ser Leu 
            20                  25                  30          


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


Ser Leu Val His Ser Asn Gly Asn Thr Tyr Leu His Trp Phe Leu Gln 
    50                  55                  60                  


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


Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
                85                  90                  95      


Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr 
            100                 105                 110         


Phe Cys Ser Gln Ser Thr His Val Pro Tyr Thr Phe Gly Gly Gly Thr 
        115                 120                 125             


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


Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val 
145                 150                 155                 160 


Lys Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Val Ser Gly Phe Thr 
                165                 170                 175     


Phe Ser Asn Tyr Ala Met Ser Trp Val Arg Gln Thr Pro Glu Thr Arg 
            180                 185                 190         


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


Pro Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys 
    210                 215                 220                 


Asp Thr Leu Tyr Leu Gln Met Ser Ser Leu Arg Ser Glu Asp Thr Ala 
225                 230                 235                 240 


Met Tyr Tyr Cys Val Arg Gln Arg Val Gly Asp Tyr Val Ser Ser Leu 
                245                 250                 255     


Leu Gly Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Ala Ser 
            260                 265                 270         


Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Pro Val 
        275                 280                 285             


Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
    290                 295                 300                 


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
305                 310                 315                 320 


Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
                325                 330                 335     


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Gln Ser Thr 
            340                 345                 350         


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
        355                 360                 365             


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser 
    370                 375                 380                 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
385                 390                 395                 400 


Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val 
                405                 410                 415     


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
            420                 425                 430         


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
        435                 440                 445             


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr 
    450                 455                 460                 


Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val 
465                 470                 475                 480 


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
                485                 490                 495     


Ser Leu Gly Lys Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly 
            500                 505                 510         


Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg 
        515                 520                 525             


Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln 
    530                 535                 540                 


Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu 
545                 550                 555                 560 


Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala 
                565                 570                 575     


Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu 
            580                 585                 590         


Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp 
        595                 600                 605             


Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu 
    610                 615                 620                 


Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile 
625                 630                 635                 640 


Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr 
                645                 650                 655     


Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met 
            660                 665                 670         


Gln Ala Leu Pro Pro Arg 
        675             


<210>  16
<211>  678
<212>  PRT
<213>  Artificial sequence

<220>
<223>   CD8Leader-anti-BioVH/VL- IgG4Hinge+CH2+CH3-CD8TM-41BB-CD3z

<400>  16

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 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu 
            20                  25                  30          


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


Thr Phe Ser Asn Tyr Ala Met Ser Trp Val Arg Gln Thr Pro Glu Thr 
    50                  55                  60                  


Arg Leu Asn Trp Val Ala Thr Ile Thr Gly Gly Gly Ser Tyr Thr Tyr 
65                  70                  75                  80  


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


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


Ala Met Tyr Tyr Cys Val Arg Gln Arg Val Gly Asp Tyr Val Ser Ser 
        115                 120                 125             


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


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Val 
145                 150                 155                 160 


Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly Asp Gln 
                165                 170                 175     


Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser Asn Gly 
            180                 185                 190         


Asn Thr Tyr Leu His Trp Phe Leu Gln Lys Pro Gly Gln Ser Pro Asn 
        195                 200                 205             


Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro Asp Arg 
    210                 215                 220                 


Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg 
225                 230                 235                 240 


Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Ser Thr His 
                245                 250                 255     


Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Ala Ser 
            260                 265                 270         


Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Pro Val 
        275                 280                 285             


Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
    290                 295                 300                 


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
305                 310                 315                 320 


Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
                325                 330                 335     


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Gln Ser Thr 
            340                 345                 350         


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
        355                 360                 365             


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser 
    370                 375                 380                 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
385                 390                 395                 400 


Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val 
                405                 410                 415     


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
            420                 425                 430         


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
        435                 440                 445             


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr 
    450                 455                 460                 


Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val 
465                 470                 475                 480 


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
                485                 490                 495     


Ser Leu Gly Lys Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly 
            500                 505                 510         


Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg 
        515                 520                 525             


Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln 
    530                 535                 540                 


Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu 
545                 550                 555                 560 


Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala 
                565                 570                 575     


Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu 
            580                 585                 590         


Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp 
        595                 600                 605             


Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu 
    610                 615                 620                 


Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile 
625                 630                 635                 640 


Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr 
                645                 650                 655     


Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met 
            660                 665                 670         


Gln Ala Leu Pro Pro Arg 
        675             


<210>  17
<211>  774
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CD8Leader-anti-BioVL/VH-CH1+IgG4Hinge+CH2+CH3-CD8TM-41BB-CD3z

<400>  17

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 Val Val Met Thr Gln Thr Pro Leu Ser Leu 
            20                  25                  30          


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


Ser Leu Val His Ser Asn Gly Asn Thr Tyr Leu His Trp Phe Leu Gln 
    50                  55                  60                  


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


Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
                85                  90                  95      


Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr 
            100                 105                 110         


Phe Cys Ser Gln Ser Thr His Val Pro Tyr Thr Phe Gly Gly Gly Thr 
        115                 120                 125             


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


Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val 
145                 150                 155                 160 


Lys Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Val Ser Gly Phe Thr 
                165                 170                 175     


Phe Ser Asn Tyr Ala Met Ser Trp Val Arg Gln Thr Pro Glu Thr Arg 
            180                 185                 190         


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


Pro Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys 
    210                 215                 220                 


Asp Thr Leu Tyr Leu Gln Met Ser Ser Leu Arg Ser Glu Asp Thr Ala 
225                 230                 235                 240 


Met Tyr Tyr Cys Val Arg Gln Arg Val Gly Asp Tyr Val Ser Ser Leu 
                245                 250                 255     


Leu Gly Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Ala Ser 
            260                 265                 270         


Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Arg Ser Thr 
        275                 280                 285             


Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro 
    290                 295                 300                 


Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val 
305                 310                 315                 320 


His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser 
                325                 330                 335     


Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr 
            340                 345                 350         


Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val 
        355                 360                 365             


Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Pro Val 
    370                 375                 380                 


Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
385                 390                 395                 400 


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                405                 410                 415     


Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
            420                 425                 430         


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Gln Ser Thr 
        435                 440                 445             


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    450                 455                 460                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser 
465                 470                 475                 480 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                485                 490                 495     


Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val 
            500                 505                 510         


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        515                 520                 525             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    530                 535                 540                 


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr 
545                 550                 555                 560 


Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val 
                565                 570                 575     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            580                 585                 590         


Ser Leu Gly Lys Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly 
        595                 600                 605             


Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg 
    610                 615                 620                 


Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln 
625                 630                 635                 640 


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


Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala 
            660                 665                 670         


Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu 
        675                 680                 685             


Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp 
    690                 695                 700                 


Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu 
705                 710                 715                 720 


Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile 
                725                 730                 735     


Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr 
            740                 745                 750         


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


Gln Ala Leu Pro Pro Arg 
    770                 


<210>  18
<211>  774
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CD8Leader-anti-BioVH/VL-CH1+IgG4Hinge+CH2+CH3-CD8TM-41BB-CD3z

<400>  18

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 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu 
            20                  25                  30          


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


Thr Phe Ser Asn Tyr Ala Met Ser Trp Val Arg Gln Thr Pro Glu Thr 
    50                  55                  60                  


Arg Leu Asn Trp Val Ala Thr Ile Thr Gly Gly Gly Ser Tyr Thr Tyr 
65                  70                  75                  80  


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


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


Ala Met Tyr Tyr Cys Val Arg Gln Arg Val Gly Asp Tyr Val Ser Ser 
        115                 120                 125             


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


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Val 
145                 150                 155                 160 


Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly Asp Gln 
                165                 170                 175     


Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser Asn Gly 
            180                 185                 190         


Asn Thr Tyr Leu His Trp Phe Leu Gln Lys Pro Gly Gln Ser Pro Asn 
        195                 200                 205             


Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro Asp Arg 
    210                 215                 220                 


Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg 
225                 230                 235                 240 


Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Ser Thr His 
                245                 250                 255     


Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Ala Ser 
            260                 265                 270         


Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Arg Ser Thr 
        275                 280                 285             


Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro 
    290                 295                 300                 


Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val 
305                 310                 315                 320 


His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser 
                325                 330                 335     


Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr 
            340                 345                 350         


Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val 
        355                 360                 365             


Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Pro Val 
    370                 375                 380                 


Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
385                 390                 395                 400 


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                405                 410                 415     


Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
            420                 425                 430         


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Gln Ser Thr 
        435                 440                 445             


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    450                 455                 460                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser 
465                 470                 475                 480 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                485                 490                 495     


Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val 
            500                 505                 510         


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        515                 520                 525             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    530                 535                 540                 


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr 
545                 550                 555                 560 


Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val 
                565                 570                 575     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            580                 585                 590         


Ser Leu Gly Lys Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly 
        595                 600                 605             


Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg 
    610                 615                 620                 


Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln 
625                 630                 635                 640 


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


Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala 
            660                 665                 670         


Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu 
        675                 680                 685             


Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp 
    690                 695                 700                 


Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu 
705                 710                 715                 720 


Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile 
                725                 730                 735     


Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr 
            740                 745                 750         


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


Gln Ala Leu Pro Pro Arg 
    770                 


<210>  19
<211>  569
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CD8Leader-anti-BioVL/VH-IgG4Hinge+CH3-CD8TM-41BB-CD3z

<400>  19

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 Val Val Met Thr Gln Thr Pro Leu Ser Leu 
            20                  25                  30          


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


Ser Leu Val His Ser Asn Gly Asn Thr Tyr Leu His Trp Phe Leu Gln 
    50                  55                  60                  


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


Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
                85                  90                  95      


Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr 
            100                 105                 110         


Phe Cys Ser Gln Ser Thr His Val Pro Tyr Thr Phe Gly Gly Gly Thr 
        115                 120                 125             


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


Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val 
145                 150                 155                 160 


Lys Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Val Ser Gly Phe Thr 
                165                 170                 175     


Phe Ser Asn Tyr Ala Met Ser Trp Val Arg Gln Thr Pro Glu Thr Arg 
            180                 185                 190         


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


Pro Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys 
    210                 215                 220                 


Asp Thr Leu Tyr Leu Gln Met Ser Ser Leu Arg Ser Glu Asp Thr Ala 
225                 230                 235                 240 


Met Tyr Tyr Cys Val Arg Gln Arg Val Gly Asp Tyr Val Ser Ser Leu 
                245                 250                 255     


Leu Gly Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Ala Ser 
            260                 265                 270         


Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Gly Gln Pro Arg 
        275                 280                 285             


Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys 
    290                 295                 300                 


Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
305                 310                 315                 320 


Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                325                 330                 335     


Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
            340                 345                 350         


Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser 
        355                 360                 365             


Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
    370                 375                 380                 


Leu Ser Leu Ser Leu Gly Lys Ile Tyr Ile Trp Ala Pro Leu Ala Gly 
385                 390                 395                 400 


Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys 
                405                 410                 415     


Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg 
            420                 425                 430         


Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro 
        435                 440                 445             


Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser 
    450                 455                 460                 


Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu 
465                 470                 475                 480 


Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg 
                485                 490                 495     


Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln 
            500                 505                 510         


Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr 
        515                 520                 525             


Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp 
    530                 535                 540                 


Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala 
545                 550                 555                 560 


Leu His Met Gln Ala Leu Pro Pro Arg 
                565                 


<210>  20
<211>  569
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CD8Leader-anti-BioVH/VL-IgG4Hinge+CH3-CD8TM-41BB-CD3z

<400>  20

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 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu 
            20                  25                  30          


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


Thr Phe Ser Asn Tyr Ala Met Ser Trp Val Arg Gln Thr Pro Glu Thr 
    50                  55                  60                  


Arg Leu Asn Trp Val Ala Thr Ile Thr Gly Gly Gly Ser Tyr Thr Tyr 
65                  70                  75                  80  


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


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


Ala Met Tyr Tyr Cys Val Arg Gln Arg Val Gly Asp Tyr Val Ser Ser 
        115                 120                 125             


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


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Val 
145                 150                 155                 160 


Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly Asp Gln 
                165                 170                 175     


Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser Asn Gly 
            180                 185                 190         


Asn Thr Tyr Leu His Trp Phe Leu Gln Lys Pro Gly Gln Ser Pro Asn 
        195                 200                 205             


Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro Asp Arg 
    210                 215                 220                 


Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg 
225                 230                 235                 240 


Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Ser Thr His 
                245                 250                 255     


Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Ala Ser 
            260                 265                 270         


Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Gly Gln Pro Arg 
        275                 280                 285             


Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys 
    290                 295                 300                 


Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
305                 310                 315                 320 


Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                325                 330                 335     


Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
            340                 345                 350         


Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser 
        355                 360                 365             


Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
    370                 375                 380                 


Leu Ser Leu Ser Leu Gly Lys Ile Tyr Ile Trp Ala Pro Leu Ala Gly 
385                 390                 395                 400 


Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys 
                405                 410                 415     


Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg 
            420                 425                 430         


Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro 
        435                 440                 445             


Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser 
    450                 455                 460                 


Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu 
465                 470                 475                 480 


Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg 
                485                 490                 495     


Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln 
            500                 505                 510         


Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr 
        515                 520                 525             


Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp 
    530                 535                 540                 


Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala 
545                 550                 555                 560 


Leu His Met Gln Ala Leu Pro Pro Arg 
                565                 


