公开(公告)号：US20210371542A1

公开(公告)日：2021-12-02

申请号：US16762459

申请日：2018-11-07

申请人： The U.S.A., as represented by the Secretary, Department of Health and Human Services

发明人： Mitchell Ho ,  Nan Li ,  Dan Li

IPC分类号： C07K16/30 ,  C07K14/715 ,  C07K14/71 ,  C07K14/705 ,  C07K14/725 ,  A61K35/17 ,  A61P35/00

摘要： Nucleic acid constructs encoding a chimeric antigen receptor (CAR) and a truncated human epidermal growth factor receptor (huEGFRt) are described. The encoded CARs include a tumor antigen-specific monoclonal antibody, such as a glypican-3 (GPC3)-specific, a GPC2-specific or a mesothelin-specific monoclonal antibody, fused to a CD8α hinge region, a CD8α transmembrane region, a 4-1BB co-stimulatory domain and a CD3ζ signaling domain. Isolated host cells, such as isolated T cells that co-express the disclosed CARs and huEGFRt are also described. T cells transduced with the disclosed CAR constructs can be used for cancer immunotherapy.

公开(公告)号：US12122843B2

公开(公告)日：2024-10-22

申请号：US17422609

申请日：2020-01-15

申请人： The U.S.A., as represented by the Secretary, Department of Health and Human Services

发明人： Mitchell Ho ,  Nan Li ,  Jiajia Pan

IPC分类号： C07K16/30 ,  A61K39/00 ,  A61K47/68 ,  A61K47/69 ,  A61P35/04 ,  C07K14/47

CPC分类号： C07K16/303 ,  A61K47/6829 ,  A61K47/6929 ,  A61P35/04 ,  C07K14/4725 ,  A61K2039/505

摘要： Monoclonal antibodies that specifically bind glypican-1 (GPC1) are described. Chimeric antigen receptor (CAR) T cells, immunotoxins and other antibody conjugates based on the GPC1-specific antibodies are also described. The disclosed CAR T cells, immunotoxins, GPC1-specific antibodies and conjugates thereof can be used, for example, in the diagnosis or treatment of GPC1-positive pancreatic cancer and other cancers.

公开(公告)号：US20230406953A1

公开(公告)日：2023-12-21

申请号：US18359071

申请日：2023-07-26

申请人： The U.S.A., as represented by the Secretary, Department of Health and Human Services

发明人： Mitchell Ho ,  Nan Li ,  Dan Li

IPC分类号： C07K16/30 ,  A61P35/00 ,  A61K35/17 ,  C07K14/725 ,  C07K14/705 ,  C07K14/71 ,  C07K14/715

CPC分类号： C07K16/303 ,  A61P35/00 ,  A61K35/17 ,  C07K14/7051 ,  C07K14/70517 ,  C07K14/70521 ,  C07K14/70578 ,  C07K14/71 ,  C07K14/7153 ,  A61K2039/505

摘要： Nucleic acid constructs encoding a chimeric antigen receptor (CAR) and a truncated human epidermal growth factor receptor (huEGFRt) are described. The encoded CARs include a tumor antigen-specific monoclonal antibody, such as a glypican-3 (GPC3)-specific, a GPC2-specific or a mesothelin-specific monoclonal antibody, fused to a CD8α hinge region, a CD8α transmembrane region, a 4-1BB co-stimulatory domain and a CD3ζ signaling domain. Isolated host cells, such as isolated T cells that co-express the disclosed CARs and huEGFRt are also described. T cells transduced with the disclosed CAR constructs can be used for cancer immunotherapy.

公开(公告)号：US11802163B2

公开(公告)日：2023-10-31

申请号：US16762459

申请日：2018-11-07

申请人： The U.S.A., as represented by the Secretary, Department of Health and Human Services

发明人： Mitchell Ho ,  Nan Li ,  Dan Li

IPC分类号： C07K16/30 ,  A61P35/00 ,  A61K35/17 ,  C07K14/725 ,  C07K14/705 ,  C07K14/71 ,  C07K14/715 ,  A61K39/00

CPC分类号： C07K16/303 ,  A61K35/17 ,  A61P35/00 ,  C07K14/7051 ,  C07K14/70517 ,  C07K14/70521 ,  C07K14/70578 ,  C07K14/71 ,  C07K14/7153 ,  A61K2039/505 ,  C07K2317/569 ,  C07K2317/622 ,  C07K2319/02 ,  C07K2319/03

摘要： Nucleic acid constructs encoding a chimeric antigen receptor (CAR) and a truncated human epidermal growth factor receptor (huEGFRt) are described. The encoded CARs include a tumor antigen-specific monoclonal antibody, such as a glypican-3 (GPC3)-specific, a GPC2-specific or a mesothelin-specific monoclonal antibody, fused to a CD8α hinge region, a CD8α transmembrane region, a 4-1BB co-stimulatory domain and a CD3ζ signaling domain. Isolated host cells, such as isolated T cells that co-express the disclosed CARs and huEGFRt are also described. T cells transduced with the disclosed CAR constructs can be used for cancer immunotherapy.

公开(公告)号：US20230340146A1

公开(公告)日：2023-10-26

申请号：US18020191

申请日：2021-08-10

申请人： The U.S.A, as represented by the Secretary, Department of Health and Human Services

发明人： Mitchell Ho ,  Nan Li ,  Jessica Diana Hong

IPC分类号： C07K14/725 ,  C12N15/86 ,  C07K16/30 ,  A61P35/00

CPC分类号： C07K16/303 ,  A61P35/00 ,  C07K14/7051 ,  C12N15/86 ,  C07K2317/53 ,  C07K2317/565 ,  C07K2317/569 ,  C07K2317/622 ,  C07K2319/02 ,  C07K2319/03

摘要： Optimized chimeric antigen receptors (CARs) targeting glypican-1 (GPC1) that include a 12-amino acid hinge region from IgG4 are described. The optimized CARs include a transmembrane domain from either CD8 or CD28. Immune cells, such as T cells or natural killer cells, expressing the optimized CARs can be used to treat GPC1-positive solid tumors.

公开(公告)号：US20240301084A1

公开(公告)日：2024-09-12

申请号：US18661979

申请日：2024-05-13

申请人： The U.S.A., as represented by the Secretary, Department of Health and Human Services

发明人： Mitchell Ho ,  Nan Li ,  Bryan D. Fleming

IPC分类号： C07K16/30 ,  A61K39/00 ,  A61K47/68 ,  A61P35/00 ,  C07K14/725 ,  C12N15/86 ,  G01N33/574

CPC分类号： C07K16/30 ,  A61K47/6829 ,  A61P35/00 ,  C07K14/7051 ,  C12N15/86 ,  G01N33/5748 ,  A61K2039/505

摘要： Monoclonal antibodies that bind glypican-2 (GPC2) with high affinity are described. Immunotoxins and chimeric antigen receptors (CARs) that include the disclosed antibodies or antigen-binding fragments thereof are further described. In some instances, the antibody or antigen-binding fragment is humanized. The disclosed GPC2-specific antibodies and conjugates can be used, for example, for the diagnosis or treatment of GPC2-positive cancers, including neuroblastoma, medulloblastoma and retinoblastoma.

公开(公告)号：US11066479B2

公开(公告)日：2021-07-20

申请号：US16322712

申请日：2017-07-20

申请人： The U.S.A., as represented by the Secretary, Department of Health and Human Services

发明人： Mitchell Ho ,  Nan Li ,  Dimiter S. Dimitrov

IPC分类号： C07K16/30 ,  A61K47/69 ,  A61K47/64 ,  A61P35/00 ,  C07K7/08 ,  C07K16/28

摘要： A panel of human variable heavy (VH) single domain monoclonal antibodies specific for cell-surface glypican-2 (GPC2) are described. Methods for the diagnosis and treatment and GPC2-positive cancer are also described. Recombinant immunotoxins comprised of a GPC2-specific VH domain antibody and a clinically used form of Pseudomonas exotoxin A (PE38) were generated and shown to inhibit GPC2-positive neuroblastoma tumor cell growth and inhibit neuroblastoma xenograft growth in nude mice, without significant toxicity. Chimeric antigen receptors comprising a GPC2-specific VH single domain antibody are also described. T cells expressing the GPC2-specific CARs potently killed GPC2-positive neuroblastoma cells in a dose-dependent manner.

公开(公告)号：US12012463B2

公开(公告)日：2024-06-18

申请号：US17266419

申请日：2019-08-06

申请人： The U.S.A., as represented by the Secretary, Department of Health and Human Services

发明人： Mitchell Ho ,  Nan Li ,  Bryan D. Fleming

IPC分类号： C07K16/30 ,  A61K47/68 ,  A61P35/00 ,  C07K14/725 ,  C12N15/86 ,  G01N33/574 ,  A61K39/00

CPC分类号： C07K16/30 ,  A61K47/6829 ,  A61P35/00 ,  C07K14/7051 ,  C12N15/86 ,  G01N33/5748 ,  A61K2039/505

摘要： Monoclonal antibodies that bind glypican-2 (GPC2) with high affinity are described. Immunotoxins and chimeric antigen receptors (CARs) that include the disclosed antibodies or antigen-binding fragments thereof are further described. In some instances, the antibody or antigen-binding fragment is humanized. The disclosed GPC2-specific antibodies and conjugates can be used, for example, for the diagnosis or treatment of GPC2-positive cancers, including neuroblastoma, medulloblastoma and retinoblastoma.

公开(公告)号：US20220064324A1

公开(公告)日：2022-03-03

申请号：US17421334

申请日：2020-01-02

申请人： The U.S.A., as represented by the Secretary, Department of Health and Human Services

发明人： Mitchell Ho ,  Ira H. Pastan ,  Jessica D. Hong ,  Nan Li

IPC分类号： C07K16/30 ,  C07K14/705 ,  C07K14/725 ,  A61K47/68 ,  C07K16/28 ,  A61K47/69 ,  C07K14/715 ,  C07K14/71 ,  A61P35/00

摘要： Camel single-domain monoclonal antibodies that specifically bind human and mouse mesothelin are described. Chimeric antigen receptor (CAR) T cells and antibody conjugates based on the mesothelin-specific antibodies are also described. The disclosed CAR T cells, mesothelin-specific antibodies and conjugates thereof can be used, for example, in the diagnosis or treatment of mesothelin-positive cancers.

公开(公告)号：US20210292428A1

公开(公告)日：2021-09-23

申请号：US17266419

申请日：2019-08-06

申请人： The U.S.A., as represented by the Secretary, Department of Health and Human Services

发明人： Mitchell Ho ,  Nan Li ,  Bryan D. Fleming

IPC分类号： C07K16/30 ,  C07K14/725 ,  A61K47/68 ,  G01N33/574 ,  C12N15/86 ,  A61P35/00

摘要： Monoclonal antibodies that bind glypican-2 (GPC2) with high affinity are described. Immunotoxins and chimeric antigen receptors (CARs) that include the disclosed antibodies or antigen-binding fragments thereof are further described. In some instances, the antibody or antigen-binding fragment is humanized. The disclosed GPC2-specific antibodies and conjugates can be used, for example, for the diagnosis or treatment of GPC2-positive cancers, including neuroblastoma, medulloblastoma and retinoblastoma.