Compositions and methods for inhibition of lineage specific antigens

Patent metadata

Field	Value
Publication number	US-10660919-B2
Application number	US-201816174089-A
Country	US
Kind code	B2
Filing date	Oct 29, 2018
Priority date	Oct 16, 2015
Publication date	May 26, 2020
Grant date	May 26, 2020

Abstract

Disclosed herein are methods of administering an agent targeting a lineage-specific cell-surface antigen and a population of hematopoietic cells that are deficient in the lineage-specific cell-surface antigen for immunotherapy of hematological malignancies.

First claim

What is claimed is:

1. A method of treating a hematopoietic malignancy in a subject in need thereof, the method comprising
administering to the subject an effective amount of a population of genetically engineered human hematopoietic cells, wherein the hematopoietic cells are engineered such that they are deficient in the expression of a lineage-specific cell-surface antigen which is expressed by their naturally-occurring hematopoietic cell counterpart, and
wherein the genetically engineered hematopoietic cells are hematopoietic stem cells, hematopoietic progenitor cells, or a combination thereof,
wherein the hematopoietic cells do not comprise a chimeric antigen receptor,
wherein the lineage-specific cell-surface antigen is CD33, and
wherein an endogenous gene encoding the lineage-specific cell-surface antigen is disrupted using genome editing.

2. The method of claim 1 , wherein the genetically engineered human hematopoietic cells are hematopoietic stem cells.

3. The method of claim 1 , wherein the human hematopoietic cells are obtained from bone marrow, blood, umbilical cord, or peripheral blood mononuclear cells (PBMCs) of a human subject.

4. The method of claim 1 , wherein the whole or a portion of the endogenous gene encoding the lineage-specific cell-surface antigen is deleted.

5. The method of claim 1 , wherein the level of the lineage-specific cell-surface antigen is reduced as compared with the level of the lineage-specific cell-surface antigen expressed by its naturally-occurring hematopoietic cell counterpart.

6. The method of claim 1 , wherein the genome editing is a CRISPR system.

7. The method of claim 6 , wherein the CRISPR system comprises a guide nucleic acid that hybridizes to a coding or non-coding sequence of the endogenous gene encoding the lineage-specific cell-surface antigen.

8. The method of claim 6 , wherein the CRISPR system cleaves or produces an insertion, deletion and/or substitution of one or more nucleotides in a coding region or a non-coding region of an endogenous gene encoding the lineage-specific cell-surface antigen.

9. The method of claim 1 , further comprising
administering to the subject an effective amount of an agent that targets the lineage-specific cell-surface antigen that is deficient in the hematopoietic cells, wherein the agent comprises an antigen-binding fragment that binds said lineage-specific cell-surface antigen.

10. The method of claim 9 , wherein the agent is an antibody or antibody fragment selected from the group consisting of a monoclonal antibody, fully human antibody, humanized antibody, chimeric antibody, single-chain antibody, bi-specific antibody, and a F(ab') 2 fragment.

11. The method of claim 9 , wherein the agent is an immune cell expressing a chimeric receptor that comprises said antigen-binding fragment.

12. The method of claim 11 , wherein the immune cell expressing a chimeric receptor is a T cell and wherein the antigen-binding fragment binds CD 33 .

13. The method of claim 9 , wherein the hematopoietic malignancy is selected from the group consisting of Hodgkin's lymphoma, non-Hodgkin's lymphoma, leukemia, acute myeloid leukemia, chronic myelogenous leukemia, acute lymphoblastic leukemia, chronic lymphoblastic leukemia, and multiple myeloma.

Assignees

• Univ Columbia

Inventors

• Mukherjee Siddhartha
• Borot Florence
• Ali Abdullah Mahmood

Classifications

• C07K16/2803 Primary

  against the immunoglobulin superfamily · CPC title

• A61K35/28 Primary

  Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells · CPC title

• A61K2035/124

  the cells being hematopoietic, bone marrow derived or blood cells · CPC title

• C12N5/0647

  Haematopoietic stem cells; Uncommitted or multipotent progenitors · CPC title

• C07K16/30

  from tumour cells · CPC title