Methods of treatments using antigen-binding proteins targeting CD56

Patent metadata

Field	Value
Publication number	US-12018077-B2
Application number	US-202016912291-A
Country	US
Kind code	B2
Filing date	Jun 25, 2020
Priority date	Jul 31, 2015
Publication date	Jun 25, 2024
Grant date	Jun 25, 2024

Abstract

The presently disclosed subject matter provides for methods and compositions for treating cancer (e.g., multiple myeloma). It relates to anti-CD56 antibodies, chimeric antigen receptors (CARs) that specifically target human CD56, and immunoresponsive cells comprising such CARs. The presently disclosed CD56-specific CARs have enhanced immune-activating properties, including anti-tumor activity.

First claim

What is claimed is:

1. A method of reducing tumor burden in a subject, and/or increasing or lengthening survival of a subject having a neoplasm, and/or treating a neoplasm in a subject, wherein the neoplasm and/or tumor is associated with overexpression of CD56, the method comprising
administering to the subject an effective amount of immunoresponsive cells, or a pharmaceutical composition comprising thereof, wherein the immunoresponsive cell comprises a chimeric antigen receptor (CAR), comprising an extracellular antigen-binding domain that binds to human CD56, a transmembrane domain, and an intracellular domain, wherein the extracellular antigen-binding domain comprises a heavy chain variable region and a light chain variable region, wherein:
(a) the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 1, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 3; and the light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 5, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 6;
(b) the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 1, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 59; the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 5, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 6;
(c) the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 9, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 10, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 11; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 15;
(d) the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 9, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 10, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 11; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 16;
(e) the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 9, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 10, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 11; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 17; or
(f) the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 9, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 10, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 11; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 13, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 18.

2. The method of claim 1 , wherein the neoplasm and/or tumor is selected from the group consisting of multiple myeloma, neuroblastoma, glioma, acute myeloid leukemia, colon cancer, pancreatic cancer, thyroid cancer, small cell lung cancer, and NK cell lymphoma.

3. The method of claim 2 , wherein the neoplasm and/or tumor is multiple myeloma.

4. The method of claim 1 , wherein the method reduces or eradicates tumor burden in the subject.

5. The method of claim 1 , wherein the subject is a human.

6. The method of claim 1 , wherein the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 1, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 3; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 5, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 6.

7. The method of claim 1 , wherein the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 1, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 59; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 5, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 6.

8. The method of claim 1 , wherein:
(i) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:7; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:8;
(ii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 19; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 20;
(iii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 21; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 22;
(iv) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 23; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 24; or
(v) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 25; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 26.

9. The method of claim 8 , wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:7; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:8.

10. The method of claim 1 , wherein the extracellular antigen-binding domain comprises a single-chain variable fragment (scFv), a Fab that is optionally crosslinked, or a F(ab) 2 .

11. The method of claim 10 , wherein the scFv, Fab, or F(ab) 2 is comprised in a fusion protein with a heterologous sequence to form the extracellular antigen-binding domain.

12. The method of claim 1 , wherein the extracellular antigen-binding domain comprises a human scFv.

13. The method of claim 1 , wherein the extracellular antigen-binding domain comprises a linker between the heavy chain variable region and the light chain variable region.

14. The method of claim 1 , wherein a signal peptide that is covalently joined to the 5′ terminus of the extracellular antigen-binding domain.

15. The method of claim 1 , the transmembrane domain comprises a CD8 polypeptide, a CD28 polypeptide, a CD3ζ polypeptide, a CD4 polypeptide, a 4-1BB polypeptide, an OX40 polypeptide, an ICOS polypept

Assignees

• Memorial Sloan Kettering Cancer Center
• Us Health
• Us Health

Inventors

• Sadelain Michel
• Benjamin Reuben
• Dimitrov Dimiter S
• Feng Yang

Classifications

• A61K40/4276

  Prostate specific membrane antigen [PSMA] · CPC title

• A61K40/4261

  Proteoglycans, e.g. glypican, brevican or CSPG4 · CPC title

• A61K40/4254

  Adhesion molecules, e.g. NRCAM, EpCAM or cadherins · CPC title

• A61K40/4211

  CD19 or B4 · CPC title

• A61K40/418

  Antigens related to induction of tolerance to non-self · CPC title