Treatment of cancer using a CD33 chimeric antigen receptor

Patent metadata

Field	Value
Publication number	US-12338287-B2
Application number	US-202017083211-A
Country	US
Kind code	B2
Filing date	Oct 28, 2020
Priority date	Jul 21, 2014
Publication date	Jun 24, 2025
Grant date	Jun 24, 2025

Abstract

The invention provides compositions and methods for treating diseases associated with expression of CD33. The invention also relates to chimeric antigen receptor (CAR) specific to CD33, vectors encoding the same, and recombinant T cells comprising the CD33 CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a CD33 binding domain.

First claim

What is claimed is:

1. A method of inducing an immune response in a mammal, comprising administering to the mammal an effective amount of a population of immune effector cells comprising a chimeric antigen receptor (CAR) polypeptide, wherein the CAR polypeptide comprises a CD33 binding domain, a transmembrane domain, and an intracellular signaling domain, wherein the intracellular domain comprises a costimulatory domain, a primary signaling domain, or both a costimulatory domain and a primary signaling domain, and wherein said CD33 binding domain comprises a heavy chain variable region and a light chain variable region selected from the group consisting of:
(i) a heavy chain variable region comprising:
a heavy chain complementary determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO: 274, a heavy chain complementary determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO: 283, and a heavy chain complementary determining region 3 (HC CDR3) comprising the sequence of SEQ ID NO:292 present in order of HC CDR1, HC CDR2, and HC CDR3; and
a light chain variable region comprising:
a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO: 301, a light chain complementarity determining region 2 (LC CDR2) comprising the sequence of SEQ ID NO: 310, and a light chain complementarity determining region 3 (LC CDR3) comprising the sequence of SEQ ID NO:319 present in order of LC CDR1, LC CDR2, and LC CDR3;
(ii) a heavy chain variable region comprising:
a heavy chain complementarity determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO: 328, a heavy chain complementarity determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO: 337, and a heavy chain complementarity determining region 3 (HC CDR3) comprising the sequence of SEQ ID NO:346 present in order of HC CDR1, HC CDR2, and HC CDR3; and
a light chain variable region comprising:
a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO: 355, a light chain complementarity determining region 2 (LC CDR2) comprising the sequence of SEQ ID NO: 364, and a light chain complementarity determining region 3 (LC CDR3) comprising the sequence of SEQ ID NO:373 present in order of LC CDR1, LC CDR2, and LC CDR3; and
(iii) a heavy chain variable region comprising:
a heavy chain complementarity determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO: 89, a heavy chain complementarity determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO: 98, and a heavy chain complementarity determining region 3 (HC CDR3) comprising the sequence of SEQ ID NO: 107, present in order of HC CDR1, HC CDR2, and HC CDR3; and
a light chain variable region comprising:
a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO: 116, a light chain complementarity determining region 2 (LC CDR2) comprising the sequence of SEQ ID NO: 125, and a light chain complementarity determining region 3 (LC CDR3) comprising the sequence of SEQ ID NO: 134 present in order of LC CDR1, LC CDR2, and LC CDR3.

2. A method of inducing an immune response in a mammal having a disease associated with expression of CD33, comprising administering to the mammal an effective amount of a population of immune effector cells comprising a chimeric antigen receptor (CAR) polypeptide, wherein the CAR comprises a CD33 binding domain, a transmembrane domain, and an intracellular signaling domain, wherein the intracellular domain comprises comprising a costimulatory domain, a primary signaling domain, or both a costimulatory domain and a primary signaling domain, and wherein said CD33 binding domain comprises a heavy chain variable region and a light chain variable region selected from the group consisting of:
(i) a heavy chain variable region comprising:
a heavy chain complementary determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO: 274, a heavy chain complementary determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO: 283, and a heavy chain complementary determining region 3 (HC CDR3) comprising the sequence of SEQ ID NO:292 present in order of HC CDR1, HC CDR2, and HC CDR3; and
a light chain variable region comprising:
a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO: 301, a light chain complementarity determining region 2 (LC CDR2) comprising the sequence of SEQ ID NO: 310, and a light chain complementarity determining region 3 (LC CDR3) comprising the sequence of SEQ ID NO:319 present in order of LC CDR1, LC CDR2, and LC CDR3;
(ii) a heavy chain variable region comprising:
a heavy chain complementarity determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO: 328, a heavy chain complementarity determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO: 337, and a heavy chain complementarity determining region 3 (HC CDR3) comprising the sequence of SEQ ID NO:346 present in order of HC CDR1, HC CDR2, and HC CDR3; and
a light chain variable region comprising:
a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO: 355, a light chain complementarity determining region 2 (LC CDR2) comprising the sequence of SEQ ID NO: 364, and a light chain complementarity determining region 3 (LC CDR3) comprising the sequence of SEQ ID NO:373 present in order of LC CDR1, LC CDR2, and LC CDR3; and
(iii) a heavy chain variable region comprising:
a heavy chain complementarity determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO: 89, a heavy chain complementarity determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO: 98, and a heavy chain complementarity determining region 3 (HC CDR3) comprising the sequence of SEQ ID NO: 107, present in order of HC CDR1, HC CDR2, and HC CDR3; and
a light chain variable region comprising:
a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO: 116, a light chain complementarity determining region 2 (LC CDR2) comprising the sequence of SEQ ID NO: 125, and a light chain complementarity determining region 3 (LC CDR3) comprising the sequence of SEQ ID NO:134 present in order of LC CDR1, LC CDR2, and LC CDR3.

3. The method of claim 2 , wherein the CAR polypeptide is encoded by a nucleic acid comprising the sequence of SEQ ID NO: 80.

4. The method of claim 1 , wherein the CAR polypeptide comprises a light chain variable region selected from the group consisting of:
(i) the amino acid sequence of SEQ ID NO: 71; and
(ii) an amino acid sequence with 95-99% identity to the amino acid sequence of SEQ ID NO: 71.

5. The method of claim 1 , wherein the CAR polypeptide comprises a heavy chain variable region selected from the group consisting of:
(i) the amino acid sequence of SEQ ID NO: 62
(ii) an amino acid sequence with 95-99% identity to the amino acid sequence of SEQ ID NO: 62.

6. The method of claim 1 , wherein the CAR polypeptide comprises a single chain variable fragment (scFv) selected from the group consisting of: (i) the amino acid sequence of SEQ ID NO: 44 or 266; (ii) an amino acid sequence with 95-99% identity to SEQ ID NO: 44 or 266.

7. The method of claim 1 , wherein the transmembrane domain of the CAR polypeptide comprises an amino acid sequence selected from the group consisting of:
(i) the amino acid sequence of SEQ ID NO: 6; and
(ii) an amino acid sequence with 95-99% identity to the amino acid sequence of SEQ ID NO: 6.

8. The method of claim 1 , wherein the costimulatory domain of the CAR polypeptide comprises the amino acid sequence of SEQ ID NO:7, or a sequence with 95-99% identity to the amino acid sequence of SEQ ID NO:7.

9

Assignees

• Novartis Ag
• Univ Pennsylvania

Inventors

• Ebersbach Hilmar Erhard
• Huber Thomas
• Jascur Julia
• Richardson Celeste
• Singh Reshma
• Song Huijuan
• Wu Qilong
• Zhang Jiquan

Classifications

• A61K48/00

  Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy · CPC title

• C07K2319/33

  fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K16/30

  from tumour cells · CPC title

• C07K14/7151

  for tumor necrosis factor [TNF], for lymphotoxin [LT] · CPC title