US2016376375A1PendingUtilityA1

CSGP4 - Specific Chimeric Antigen Receptor for Cancer

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Assignee: BAYLOR COLLEGE MEDICINEPriority: Nov 27, 2013Filed: Nov 21, 2014Published: Dec 29, 2016
Est. expiryNov 27, 2033(~7.4 yrs left)· nominal 20-yr term from priority
Inventors:Gianpietro DottiSoldano Ferrone
A61K 2039/505C07K 2319/01C07K 14/70596C07K 14/70578C07K 2317/622C07K 14/70575C07K 14/70517C07K 14/7051C07K 16/30C07K 2319/03C07K 14/70521A61P 35/00C07K 2317/53C07K 2319/30C07K 16/3076A61K 40/4261A61K 40/31A61K 40/11A61K 35/17A61K 2239/57A61K 2239/38A61K 2239/31A61K 2239/49
63
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Claims

Abstract

Embodiments of the disclosure include methods and compositions related to chimeric antigen receptors (CAR) that target chondroitin sulfate proteoglycan-4 (CSPG4). T cells transduced with a CSPG4-specific CAR are effective for inhibition of particular cancer cells that express CSPG4. In certain embodiments, the cancer is melanoma, breast cancer, head and neck cancer, mesothelioma, glioblastoma, or renal cancer.

Claims

exact text as granted — not AI-modified
1 . A method of inhibiting proliferation of cancer cells, comprising the step of contacting the cancer cells with a therapeutically effective amount of immune cells that express a chimeric antigen receptor (CAR) that targets chondroitin sulfate proteoglycan-4 (CSPG4), wherein the cancer is not melanoma. 
     
     
         2 . The method of  claim 1 , wherein the cancer is head and neck cancer, mesothelioma, breast cancer, glioblastoma, or renal cancer 
     
     
         3 . The method of  claim 1 , wherein the cancer is a sarcoma. 
     
     
         4 . The method of  claim 1 , wherein said contacting is performed in vitro. 
     
     
         5 . The method of  claim 1 , wherein said contacting is performed in cell culture. 
     
     
         6 . The method of  claim 1 , wherein said contacting is performed in vivo, and said immune cells are cells in an individual. 
     
     
         7 . The method of  claim 1 , wherein said contacting is performed in vivo, and said immune cells are T cells in an individual. 
     
     
         8 . The method of  claim 5 , wherein said immune cells are autologous to the individual. 
     
     
         9 . The method of  claim 5 , wherein said immune cells are allogeneic to the individual. 
     
     
         10 . The method of  claim 1 , wherein said immune cells are T cells, NK cells, dendritic cells, or a mixture thereof. 
     
     
         11 . The method of  claim 1 , wherein said immune cells are T cells. 
     
     
         12 . The method of  claim 10 , wherein said T cells are CD4+ T cells. 
     
     
         13 . The method of  claim 10 , wherein said T cells are CD8+ T cells. 
     
     
         14 . The method of  claim 10 , wherein said T cells are Treg cells. 
     
     
         15 . The method of  claim 1 , wherein the CAR comprises a transmembrane domain selected from the group consisting of CD3-zeta, CD28, CD8α, CD4, or a combination thereof. 
     
     
         16 . The method of  claim 1 , wherein the CAR comprises a co-stimulatory molecule endodomain selected from the group consisting of CD28, CD27, 4-1BB, OX40 ICOS, and a combination thereof. 
     
     
         17 . The method of  claim 4 , wherein the individual has received, is receiving, or will receive an additional cancer treatment. 
     
     
         18 . The method of  claim 15 , wherein the additional cancer treatment comprises chemotherapy, immunotherapy, radiation, surgery, hormone therapy, or a combination thereof. 
     
     
         19 . The method of  claim 1 , wherein the immune cells harbor a polynucleotide that encodes the CAR. 
     
     
         20 . The method of  claim 17 , wherein the polynucleotide further comprises a suicide gene. 
     
     
         21 . A method of inhibiting proliferation of cancer cells, comprising the step of contacting the cancer cells with a therapeutically effective amount of immune cells that express a chimeric antigen receptor (CAR) that targets chondroitin sulfate proteoglycan-4 (CSPG4), wherein the CAR comprises a scFv antibody that is not derived from mAb 225.28S. 
     
     
         22 . A method of inhibiting proliferation of cancer cells, comprising the step of contacting the cancer cells with a therapeutically effective amount of immune cells that express a chimeric antigen receptor (CAR) that targets chondroitin sulfate proteoglycan-4 (CSPG4), wherein the CAR comprises a scFv 763.74 antibody. 
     
     
         23 . A method of inhibiting proliferation of cancer cells, comprising the step of contacting the cancer cells with a therapeutically effective amount of immune cells that express a chimeric antigen receptor (CAR) that targets chondroitin sulfate proteoglycan-4 (CSPG4), wherein the CAR comprises part or all of the IgG1 hinge. 
     
     
         24 . The method of  claim 23 , wherein the CAR further comprises the IgG1 C H 2 C H 3 domain. 
     
     
         25 . The method of  claim 23 , wherein the CAR comprises the CD28 transmembrane domain. 
     
     
         26 . The method of  claim 23 , wherein the CAR comprises CD28 endodomain or 4-1BB endodomain. 
     
     
         27 . The method of  claim 23 , wherein the CAR does not comprise the IgG1 C H 2 C H 3 domain. 
     
     
         28 . The method of  claim 23 , wherein the CAR comprises the hinge of IgG1, CD8 alpha transmembrane domain, and one of CD28 endodomain or 4-1BB endodomain. 
     
     
         29 . The method of  claim 23 , wherein the CAR comprises the hinge of IgG1, CD8 alpha transmembrane domain, CD28 endodomain, and 4-1BB endodomain. 
     
     
         30 . The method of  claim 23 , wherein the cancer is not melanoma or is not ovarian cancer or is not triple negative breast cancer. 
     
     
         31 . The method of  claim 23 , wherein the cancer is head and neck cancer, mesothelioma, glioblastoma, or renal cancer. 
     
     
         32 . A method of inhibiting proliferation of cancer cells, comprising the step of contacting the cancer cells with a therapeutically effective amount of immune cells that express a chimeric antigen receptor (CAR) that targets chondroitin sulfate proteoglycan-4 (CSPG4), wherein the CAR comprises the entire CD8a alpha stalk, CD8a hinge, CD8a transmembrane domain, and one of CD28 endodomain or 4-1BB endodomain. 
     
     
         33 . The method of  claim 30 , wherein the CAR comprises the entire CD8a alpha stalk, CD8a hinge, CD8a transmembrane domain, CD28 endodomain, and 4-1BB endodomain. 
     
     
         34 . The method of  claim 23 , wherein the cancer is not melanoma or is not ovarian cancer or is not triple negative breast cancer. 
     
     
         35 . The method of  claim 23 , wherein the cancer is head and neck cancer, mesothelioma, glioblastoma, or renal cancer.

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