Nucleic acids encoding chimeric T cell receptors

• US 7,446,190 B2
• Filed: 05/28/2003
• Issued: 11/04/2008
• Est. Priority Date: 05/28/2002
• Status: Active Grant

• Current Assignee: Sloan-Kettering Institute For Cancer Research (Memorial Sloan-Kettering Cancer Center)
• Original Assignee: Sloan-Kettering Institute For Cancer Research (Memorial Sloan-Kettering Cancer Center)
• Inventors: Sadelain, Michel, Maher, John, Brentjens, Renier
• Primary Examiner(s): Ouspenski; Ilia
• Application Number:
  US10/448,256
• Publication Number:
  US 20040043401A1
• Time in Patent Office: 1,987 Days
• Field of Search: None
• US Class Current: 536/23.4
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: C07K 14/7051 T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 14/70521 CD28, CD152
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/3069 Reproductive system, e.g. ovaria, uterus, testes, prostate
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

Chimeric T cell receptors (TCR) are provided that combine, in a single chimeric species, the intracellular domain of CD3 ζ-chain, a signaling region from a costimulatory protein such as CD28, and a binding element that specifically interacts with a selected target. When expressed, for example in T-lymphocytes from the individual to be treated for a condition associated with the selected target, a T cell immune response is stimulated in the individual to the target cells. The chimeric TCR'"'"'s are able to provide both the activation and the co-stimulation signals from a single molecule to more effectively direct T-lymphocyte cytotoxicity against the selected target and T-lymphocyte proliferation.

Claims

1. A nucleic acid polymer encoding a chimeric T cell receptor, said chimeric T cell receptor comprising

(a) a zeta chain portion comprising the intracellular domain of human CD3 ζ

chain,

(b) a costimulatory signaling region, and

(c) a binding element that specifically interacts with a selected target, wherein the costimulatory signaling region comprises the amino acid sequence encoded by SEQ ID NO;

6.

2. The nucleic acid polymer of claim 1, wherein the binding element is an antibody.

3. The nucleic acid polymer of claim 2, wherein the antibody is a single chain antibody.

4. The nucleic acid polymer of claim 3, wherein the single chain antibody binds to prostate specific membrane antigen.

5. The nucleic acid polymer of claim 3, wherein the single chain antibody binds to CD19.

6. The nucleic acid polymer of claim 3, wherein the encoded T cell receptor comprises binding element-costimulatory signaling region-zeta chain portion in that order.

7. The nucleic acid polymer of claim 1, wherein the zeta chain portion comprises the sequence obtained by amplification of human zeta chain DNA with the primers of SEQ ID Nos 1 and 2.

8. The nucleic acid polymer of claim 7, wherein the binding element is an antibody.

9. The nucleic acid polymer of claim 8, wherein the antibody is a single chain antibody.

10. The nucleic acid polymer of claim 9, wherein the single chain antibody binds to prostate specific membrane antigen.

11. The nucleic acid polymer of claim 9, wherein the single chain antibody binds to CD19.

12. The nucleic acid polymer of claim 9, wherein the encoded T cell receptor comprises binding element-costimulatory signaling region-zeta chain portion in that order.

13. The nucleic acid polymer of claim 1, wherein the encoded T cell receptor comprises binding element-signaling region-zeta chain portion in that order.