Chimeric antigen receptor factories and methods of use thereof
AssigneeDana-Farber Cancer Institute, Inc.
InventorsWayne A. Marasco, Quan Karen Zhu, Yufei Wang, Matthew Chang
Life of this patent
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Abstract
This invention is directed to chimeric antigen receptors and cells comprising the same, wherein the cells further secrete monoclonal antibodies locally at a tumor site.
Claims10
An engineered immune cell comprising a chimeric antigen receptor (CAR), wherein the chimeric antigen receptor comprises an extracellular ligand binding domain comprising an antibody, or antigen-binding fragment thereof wherein the antibody, or antigen-binding fragment thereof comprises an antigen binding domain specific for carbonic anhydrase XI (CAIX) and an antigen binding domain specific for cluster of differentiation 70 (CD70), wherein the antigen binding domain specific for CAIX comprises a sequence consisting of a variable heavy chain (VH), comprising a CDR1, CDR2, and CDR3, and a variable light chain (VL) comprising a CDR1, CDR2, and CDR3;
- wherein the antigen binding domain specific for CAIX is selected from the group consisting of:
- a) A VH CDR1, CDR2, and CDR3 according to SYAMS (SEQ ID NO:
- 46), AISGSGGSTYYADSVKG (SEQ ID NO:
- 66), SHSSGGFDY (SEQ ID NO:
- 86), And a VL CDR1, CDR2, and CDR3 according to TGSSSNIGRGYNVH (SEQ ID NO:
- 47), GNTNRPS (SEQ ID NO:
- 67), and QSYDSSLSAWV (SEQ ID NO:
- 87),
- b) A VH CDR1, CDR2, and CDR3 according to SYAMS (SEQ ID NO:
- 46), AISANGGTTYYADSVKG (SEQ ID NO:
- 68), NGNYRGAFDI (SEQ ID NO:
- 88), And a VL CDR1, CDR2, and CDR3 according to TGSSSNIGAGFDVH (SEQ ID NO:
- 56), GNTNRPS (SEQ ID NO:
- 67), and QSYDSRLSAWV (SEQ ID NO:
- 95),
- c) A VH CDR1, CDR2, and CDR3 according to TYAMT (SEQ ID NO:
- 44), AVSGSGGSTYYADSVKG (SEQ ID NO:
- 64), GPVLRYGFDI (SEQ ID NO:
- 84), And a VL CDR1, CDR2, and CDR2 according to TGSRSNIGADYDVH (SEQ ID NO:
- 45), ANNNRPS (SEQ ID NO:
- 65), and QSYDSSLRAWV (SEQ ID NO:
- 85),
- d) A VH CDR1, CDR2, and CDR3 according to SYAMS (SEQ ID NO:
- 46), AISANGGTTYYADSVKG (SEQ ID NO:
- 68), NGNYRGAFDI (SEQ ID NO:
- 88), And a VL CDR1, CDR2, and CDR3 according to TGSSSNIGAGYDVH (SEQ ID NO:
- 48), GNSNRPS (SEQ ID NO:
- 69), and QSYDRSLSWV (SEQ ID NO:
- 89),
- e) A VH CDR1, CDR2, and CDR3 according to GFTFSSYA (SEQ ID NO:
- 49), ISGSGGST (SEQ ID NO:
- 70), ATYGDYGSLDY (SEQ ID NO:
- 90), And a VL CDR1, CDR2, and CDR3 according to SSNIGAGYD (SEQ ID NO:
- 50), ANN, and QSYDSSLRAWV (SEQ ID NO:
- 85),
- f) A VH CDR1, CDR2, and CDR3 according to SYAMS (SEQ ID NO:
- 46), AISGSGGSTYYADSVKG (SEQ ID NO:
- 66), AAAGFDY (SEQ ID NO:
- 91), And a VL CDR1, CDR2 and CDR3 according to TGSSSNIGRGYNVH (SEQ ID NO:
- 47), DDINRPS (SEQ ID NO:
- 71), and QSYDSSLRAWV (SEQ ID NO:
- 85),
- g) A VH CDR1, CDR2, and CDR3 according to SYAMS (SEQ ID NO:
- 46), AISGSGGSTYYADSVKG (SEQ ID NO:
- 66), SHSSGGFDY (SEQ ID NO:
- 86), And a VL CDR1, CDR2, and CDR3 according to TGSSSNIGRGYNVH (SEQ ID NO:
- 47), GNTNRPS (SEQ ID NO:
- 67), and QSYDSSLSAWV (SEQ ID NO:
- 87),
- h) A VH CDR1, CDR2, and CDR3 according to NYAMT (SEQ ID NO:
- 52), LISYDGSVTHYTDSVKG (SEQ ID NO:
- 72), GSGYQE (SEQ ID NO:
- 92), And a VL CDR1, CDR2, and CDR3 according to GGNNIGSKSVE (SEQ ID NO:
- 53), YDSDRPS (SEQ ID NO:
- 73), and QVWDSSSDHHVV (SEQ ID NO:
- 93),
- i) A VH CDR1, CDR2, and CDR3 according to GFTFSNYA (SEQ ID NO:
- 54), ISYDGSVT (SEQ ID NO:
- 74), and ARGSGYQEH (SEQ ID NO:94), And a VL CDR1, CDR2, and CDR3 according to NIGSKS (SEQ ID NO:
- 55), YDS, and QVWDSSSDHHVV (SEQ ID NO:
- 93),
- j) A VH CDR1, CDR2, and CDR3 according to SYAMS (SEQ ID NO:
- 46), AISANGGTTYYADSVKG (SEQ ID NO:
- 68), NGNYRGAFDI (SEQ ID NO:
- 88), And a VL CDR1, CDR2, and CDR3 according to TGSRSNIGADYDVH (SEQ ID NO:
- 45), ANNNRPS (SEQ ID NO:
- 65), and QSYDSSLSAWV (SEQ ID NO:
- 87),
- k) A VH CDR1, CDR2, and CDR3 according to SYAMS (SEQ ID NO:
- 46), AISGSGGSTYYADSVKG (SEQ ID NO:
- 66), IGRYSSSLGY (SEQ ID NO:
- 96), And a VL CDR1, CDR2, and CDR3 according to TGSSSNIGRGYNVH (SEQ ID NO:
- 47), DNTNRPS (SEQ ID NO:
- 75), and QSYDSGLRWV (SEQ ID NO:
- 97),
- l) A VH CDR1, CDR2, and CDR3 according to SYAMS (SEQ ID NO:
- 46), AISGSGGSTYYADSVKG (SEQ ID NO:
- 66), YGDYGSLDY (SEQ ID NO:
- 98), And a VL CDR1, CDR2, and CDR3 according to TGSSSNIGAGYDVH (SEQ ID NO:
- 48), ANNNRPS (SEQ ID NO:
- 65), and QSYDSSLRAWV (SEQ ID NO:
- 85),
- m) A VH CDR1, CDR2, and CDR3 according to SYAMS (SEQ ID NO:
- 46), AISANGGTTYYADSVKG (SEQ ID NO:
- 68), NGNYRGAFDI (SEQ ID NO:
- 88), And a VL CDR1, CDR2, and CDR3 according to TGTSSNIGAGYDVH (SEQ ID NO:
- 57), GNNNRPS (SEQ ID NO:
- 76), and QSYDKSLSWV (SEQ ID NO:
- 99),
- n) A VH CDR1, CDR2, and CDR3 according to SYAMS (SEQ ID NO:
- 46), AISGSGVSTYYADSVKG (SEQ ID NO:
- 77), YCSSTSCYRGMDV (SEQ ID NO:
- 100), And a VL CDR1, CDR2, and CDR3 according to TGSSSNIGAGYDVH (SEQ ID NO:
- 48), ANNNRPS (SEQ ID NO:
- 65), and QSYDSSLRAWV (SEQ ID NO:
- 85),
- o) A VH CDR1, CDR2, and CDR3 according to SYAMS (SEQ ID NO:
- 46), AISANGGTTYYADSVKG, (SEQ ID NO:
- 68), NGNYRGAFDI (SEQ ID NO:
- 88), And a VL CDR1, CDR2, and CDR3 according to TGSSSNIGAGYDVH (SEQ ID NO:
- 48), GNNNRPS (SEQ ID NO:
- 76), and QSYDKSLTWV (SEQ ID NO:
- 101),
- p) A VH CDR1, CDR2, and CDR3 according to SYGMH (SEQ ID NO:
- 58), VISYDGSNKYYADSVKG (SEQ ID NO:
- 78), GRAARPPFDY (SEQ ID NO:
- 102), And a VL CDR1, CDR2, and CDR3 according to SGSSSNIGSNYVY (SEQ ID NO:
- 59), RNNQRPS (SEQ ID NO:
- 79), and AAWDDSLNGVV (SEQ ID NO:
- 103),
- q) A VH CDR1, CDR2, and CDR3 according to SYGMH (SEQ ID NO:
- 58), VISYDGSNKYYADSVKG (SEQ ID NO:
- 78), EAPYSSSLDAFDI (SEQ ID NO:
- 104), And a VL CDR1, CDR2, and CDR3 according to TGSSSNIGRGYNVH (SEQ ID NO:
- 47), GNSNRPS (SEQ ID NO:
- 69), and HSRDNNGHHI (SEQ ID NO:
- 105),
- r) A VH CDR1, CDR2, and CDR3 according to SYAMS (SEQ ID NO:);
- AISANGGTTYYADSVKG (SEQ ID NO:
- 68), NGNYRGAFDI (SEQ ID NO:
- 88), And a VL CDR1, CDR2, and CDR3 according to TGSSSNIGAGYDVH (SEQ ID NO:
- 48), GNSNRPS (SEQ ID NO:
- 69), and QSYDSSLSAWV (SEQ ID NO:
- 87),
- s) A VH CDR1, CDR2, and CDR3 according to IYAMS (SEQ ID NO:
- 60), AISGSGGGTYHADSVKG (SEQ ID NO:
- 80), FSAYSGYDL (SEQ ID NO:
- 106), and a VL CDR1, CDR2, and CDR3 according to TGSSSNIGRGYNVH (SEQ ID NO:
- 47), DNTNRPS (SEQ ID NO:
- 75), and QSYDSGLRWV (SEQ ID NO:
- 97),
- t) A VH CDR1, CDR2, and CDR3 according to SYAMS (SEQ ID NO:
- 46), AISANGGTTYYADSVKG (SEQ ID NO:
- 68), NGNYRGAFDI (SEQ ID NO:
- 88), And a VL CDR1, CDR2, and CDR3 according to TGSSSNIGAGFDVH (SEQ ID NO:
- 56), GNNNRPS (SEQ ID NO:
- 76), and QSYDSSLSAWV (SEQ ID NO:
- 87),
- u) A VH CDR1, CDR2, and CDR3 according to SYAMS (SEQ ID NO:
- 46), AISANGGTTYYADSVKG (SEQ ID NO:
- 68), NGNYRGAFDI (SEQ ID NO:
- 88), And a VL CDR1, CDR2, and CDR2 according to TGSSSNIGAGYDVH (SEQ ID NO:
- 48), GNTNRPS (SEQ ID NO:
- 67), and QSYDSTLRVWM (SEQ ID NO:
- 107),
- v) A VH CDR1, CDR2, and CDR3 according to KYAMS (SEQ ID NO:
- 61), GISGSGGSTYYADSVKG (SEQ ID NO:
- 81), SSRSGYFLPLDY (SEQ ID NO:
- 108), And a VL CDR1, CDR2, and CDR3 according to QGNSLRYYYPS (SEQ ID NO:
- 62), GKNNRPS (SEQ ID NO:
- 82), and SSRDNTDNRVV (SEQ ID NO:
- 109), and
- w) A VH CDR1, CDR2, and CDR3 according to SYGMH (SEQ ID NO:
- 58), AISGSGGSTYYADSVKG (SEQ ID NO:
- 66), AAVTGGFDP (SEQ ID NO:
- 110), And a VL CDR1, CDR2, and CDR3 according to GGDNIGRKSVH (SEQ ID NO:
- 63), DDRDRPS (SEQ ID NO:
- 83), and QVWDSSSKHYV (SEQ ID NO:
- 111),
- wherein the antigen binding domain specific for CD70 comprises a sequence consisting of a variable heavy chain (VH), comprising a CDR1, CDR2, and CDR3, and a variable light chain (VL) comprising a CDR1, CDR2, and CDR3, wherein the antigen binding domain specific for CD70 is selected from the group consisting of:
- a) A VH CDR1, CDR2, and CDR3 according to GFTVSNYA (SEQ ID NO:
- 158), KSGSDGRT (SEQ ID NO:
- 167), AKGIYDVTGSSFDS (SEQ ID NO:
- 174), And a VL CDR1, CDR2, and CDR3 according to SGSIASNY (SEQ ID NO:
- 160), EDN, and QSYDSGNRRV (SEQ ID NO:
- 176),
- b) A VH CDR1, CDR2, and CDR3 according to GFTFSSYA (SEQ ID NO:
- 49), ISGSGGSR (SEQ ID NO:
- 165), ARGRGGHGMDV (SEQ ID NO:170), And a VL CDR1, CDR2, and CDR3 according to SSNIGSNY (SEQ ID NO:
- 155), RNN, and AAWDDSLNGLV (SEQ ID NO:
- 171),
- c) A VH CDR1, CDR2, and CDR3 according to GGTFSSQA (SEQ ID NO:
- 156), IIPFFGVP (SEQ ID NO:
- 166), AVLKGRGNFDF (SEQ ID NO:172), And a VL CDR1, CDR2, and CDR3 according to YSVFHSPNNKNY (SEQ ID NO:
- 157), WAS, and QQRSNWPLT (SEQ ID NO:173),
- d) A VH CDR1, CDR2, and CDR3 according to GFTVSNYA (SEQ ID NO:
- 158), KSGSDGRT (SEQ ID NO:
- 167), AKGIYDVTGSSFDS (SEQ ID NO:
- 174), And a VL CDR1, CDR2, and CDR3 according to ALPKKY (SEQ ID NO:
- 159), EDS, and YSTDSSGNHKV (SEQ ID NO:
- 175),
- e) A VH CDR1, CDR2, and CDR3 according to GFTVSTSH (SEQ ID NO:
- 161), KDSGGKT (SEQ ID NO:
- 168), ARARPSDPYDGSGFDAFDI (SEQ ID NO:
- 177), And a VL CDR1, CDR2, and CDR3 according to SNNVGNQG (SEQ ID NO:
- 162), RNN, and SAWDSSLSAWV (SEQ ID NO:
- 178), and
- f) A VH CDR1, CDR2, and CDR3 according to GFIFSDYY (SEQ ID NO:
- 163), IRSRRGET (SEQ ID NO:
- 169), ARHRKSFTDLDAFDL (SEQ ID NO:
- 179), and And a VL CDR1, CDR2, and CDR3 according to QDIGTD (SEQ ID NO:
- 164), KAS, and QHFNNYPAT (SEQ ID NO:
- 180).
Dependencies are inferred from the claim text.