CS1-specific chimeric antigen receptor engineered immune effector cells

Patent metadata

Field	Value
Publication number	US-10358494-B2
Application number	US-201414888877-A
Country	US
Kind code	B2
Filing date	May 2, 2014
Priority date	May 3, 2013
Publication date	Jul 23, 2019
Grant date	Jul 23, 2019

Abstract

Disclosed herein are chimeric antigen receptors (CAR) that can specifically recognize tumor-associated antigens (TAA) on multiple myeloma (MM) cells. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with MM that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

First claim

What is claimed is:

1. A chimeric antigen receptor (CAR) polypeptide, comprising a CS1 antigen binding domain, a transmembrane domain, an intracellular signaling domain, and a co-stimulatory signaling region, wherein the CS1 antigen binding domain consists of one single-chain variable fragment (scFv) of an antibody that specifically binds CS1.

2. The polypeptide of claim 1 , wherein the costimulatory signaling region comprises the cytoplasmic domain of a costimulatory molecule selected from the group consisting of CD28 and 4-1BB.

3. The polypeptide of claim 1 , wherein the CAR polypeptide is defined by the formula:
SP-CS1-HG-TM-CSR-ISD;
wherein “SP” represents a signal peptide,
wherein “CS1” represents a CS1 antigen binding domain,
wherein “HG” represents an optional hinge domain,
wherein “TM” represents a transmembrane domain,
wherein “CSR” represents a co-stimulatory signaling region,
wherein “ISD” represents an intracellular signaling domain, and
wherein “-” represents a bivalent linker.

4. The polypeptide of claim 1 , wherein the intracellular signaling domain comprises a CD3 zeta (CD3ζ) signaling domain.

5. An isolated nucleic acid sequence encoding the recombinant polypeptide of claim 1 .

6. A vector comprising the isolated nucleic acid sequence of claim 5 .

7. An isolated cell comprising the vector of claim 6 .

8. The isolated cell of claim 7 , wherein the cell is selected from the group consisting of a T cell, a Natural Killer (NK) cell, and a cytotoxic T lymphocyte (CTL).

9. The isolated cell of claim 8 , wherein the cell exhibits an anti-tumor immunity when the antigen binding domain of the CAR binds to CS1.

10. The polypeptide of claim 1 , wherein the costimulatory molecule is CD28.

11. The polypeptide of claim 1 , wherein the costimulatory molecule is 4-1BB.

Assignees

• Ohio State Innovation Foundation

Inventors

• Yu Jianhua
• Hofmeister Craig
• Chu Jianhong

Classifications

• A61P39/00

  General protective or antinoxious agents · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• C07K14/70521

  CD28, CD152 · CPC title

• C07K2319/02

  containing a signal sequence · CPC title