Methods for selectively expanding and enriching cells transduced with chimeric antigen receptors and treating HIV infection

Patent metadata

Field	Value
Publication number	US-11034933-B2
Application number	US-201716070745-A
Country	US
Kind code	B2
Filing date	Jan 27, 2017
Priority date	Jan 28, 2016
Publication date	Jun 15, 2021
Grant date	Jun 15, 2021

Abstract

Disclosed herein are methods for selectively expanding cells expressing chimeric antigen receptors and enriching cells expressing chimeric antigen receptors in compositions and methods of treating HIV infection in subjects by administering the expanded and/or enriched cells.

First claim

What is claimed is:

1. A method of expanding and enriching cells expressing a chimeric antigen receptor (CAR) comprising a single chain antibody domain (SCA), which comprises contacting the cells with an antibody that binds the SCA domain while culturing the cells to thereby expand and enrich cells expressing the CAR, wherein the SCA comprises:
a first amino acid sequence having at least 95% sequence identity to a sequence selected from the group consisting of SEQ ID NO: 5, SEQ ID NO: 8, SEQ ID NO: 11, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 20, and SEQ ID NO: 23; and
a second amino acid sequence having at least 95% sequence identity to a sequence selected from the group consisting of SEQ ID NO: 6, SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 18, SEQ ID NO: 21, and SEQ ID NO: 24.

2. The method according to claim 1 , wherein the antibody binds the CAR with a higher binding affinity than any endogenous T cell receptors expressed by the cells.

3. The method according to claim 1 , wherein the antibody is an anti-human Fab antibody.

4. The method according to claim 3 , wherein the antibody is a non-human antibody.

5. The method according to claim 1 , wherein the antibody is an anti-IgG antibody.

6. The method according to claim 1 , wherein the cells are cultured for at least one cell passage.

7. The method according to claim 1 , wherein the cells are T cells.

8. The method according to claim 7 , wherein the T cells are CD8+ T cells.

9. A composition comprising one or more expanded and/or enriched cells produced according to claim 1 .

10. The composition according to claim 9 , wherein the one or more expanded and/or enriched cells comprise least about 50% of the total cells in the composition.

11. A method of treating an HIV infection in a subject which comprises administering to the subject a therapeutically effective amount of one or more expanded and/or enriched cells produced according to claim 1 thereby treating the subject for the HIV infection.

12. The method according to claim 1 , wherein the SCA comprises
SEQ ID NO: 5 and SEQ ID NO: 6;
SEQ ID NO: 8 and SEQ ID NO: 9;
SEQ ID NO: 11 and SEQ ID NO: 12;
SEQ ID NO: 14 and SEQ ID NO: 15;
SEQ ID NO: 17 and SEQ ID NO: 18;
SEQ ID NO: 20 and SEQ ID NO: 21; or
SEQ ID NO: 23 and SEQ ID NO: 24.

Assignees

• Univ California

Inventors

• Yang Otto O
• Ali Ayub
• Ng Hwee
• Kitchen Scott G
• Zack Jerome A
• Chen Irvin

Classifications

• C07K16/114

  Lentivirus (G), e.g. human immunodeficiency virus [HIV], feline immunodeficiency virus [FIV] or simian immunodeficiency virus [SIV] · CPC title

• C07K14/7051 Primary

  T-cell receptor (TcR)-CD3 complex · CPC title

• A61K40/46

  Viral antigens · CPC title

• A61K40/31

  Chimeric antigen receptors [CAR] · CPC title

• A61K40/11

  T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells · CPC title