CSGP4 - Specific Chimeric Antigen Receptor for Cancer

Patent metadata

Field	Value
Publication number	US-2016376375-A1
Application number	US-201415038997-A
Country	US
Kind code	A1
Filing date	Nov 21, 2014
Priority date	Nov 27, 2013
Publication date	Dec 29, 2016
Grant date	—

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.

First claim

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.

Assignees

• Baylor College Medicine

Inventors

• Dotti Gianpietro
• Ferrone Soldano

Classifications

• A61K2039/505

  comprising antibodies · CPC title

• C07K2319/01

  containing a localisation/targetting motif · CPC title

• C07K14/70596

  Molecules with a "CD"-designation not provided for elsewhere · CPC title

• C07K14/70578

  NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151) · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title