Isolated B7-H4 specific compositions and methods of use thereof

Patent metadata

Field	Value
Publication number	US-9422351-B2
Application number	US-201214356040-A
Country	US
Kind code	B2
Filing date	Nov 5, 2012
Priority date	Nov 3, 2011
Publication date	Aug 23, 2016
Grant date	Aug 23, 2016

Abstract

The present invention relates to B7-H4-specific chimeric antigen receptor compositions and methods of use thereof.

First claim

What is claimed is:

1. An isolated nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises a human anti-B7-H4 antibody or antigen binding fragment thereof and a CD3 zeta signaling domain, and wherein the human anti-B7-H4 antibody or antigen binding fragment thereof comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-4.

2. The isolated nucleic acid sequence of claim 1 , further comprising a nucleic acid sequence encoding a co-stimulatory signaling domain.

3. The isolated nucleic acid sequence of claim 2 , wherein the co-stimulatory signaling domain is selected from the group consisting of the CD28 signaling domain, the 4-1BB signaling domain, and a combination thereof.

4. The isolated nucleic acid sequence of claim 1 , wherein the human anti-B7-H4 antibody or antigen binding fragment thereof is encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 5-8.

5. An isolated chimeric antigen receptor (CAR) comprising a human anti-B7-H4 antibody or antigen binding fragment thereof and a CD3 zeta signaling domain, wherein the human anti-B7-H4 antibody or antigen binding fragment thereof comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-4.

6. The isolated CAR of claim 5 , further comprising a co-stimulatory signaling domain.

7. The isolated CAR of claim 6 , wherein the co-stimulatory signaling domain is selected from the group consisting of the CD28 signaling domain, the 4-1BB signaling domain, and a combination thereof.

8. A method of providing an anti-tumor immunity in a mammal, the method comprising administering to the mammal an effective amount of a genetically modified cell comprising an isolated nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises a human anti-B7-H4 antibody or antigen binding fragment thereof and a CD3 zeta signaling domain, and wherein the human anti-B7-H4 antibody or antigen binding fragment thereof comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-4.

9. The method of claim 8 , wherein the cell is an autologous T cell.

10. The method of claim 8 , wherein the mammal is a human.

11. A method of treating a mammal having a cancer, the method comprising administering to the mammal an effective amount of a genetically modified cell comprising an isolated nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises a human anti-B7-H4 antibody or antigen binding fragment thereof and a CD3 zeta signaling domain, and wherein the human anti-B7-H4 antibody or antigen binding fragment thereof comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-4.

12. The method of claim 11 , wherein the cancer is selected from the group consisting of liver cancer, pancreatic cancer, ovarian cancer, stomach cancer, lung cancer, endometrial cancer, hepatocellular carcinoma, and any combination thereof.

Assignees

• Univ Pennsylvania

Inventors

• Scholler Nathalie
• Dangaj Denarda
• Zhao Aizhi
• Powell Daniel J

Classifications

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• G01N33/575

  for cancer · CPC title

• C07K14/70532

  B7 molecules, e.g. CD80, CD86 · CPC title

• C07K2317/54

  F(ab')2 · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title