CS1 targeted chimeric antigen receptor-modified T cells for treatment of AL amyloidosis

Patent metadata

Field	Value
Publication number	US-11744862-B2
Application number	US-201816496271-A
Country	US
Kind code	B2
Filing date	Mar 20, 2018
Priority date	Mar 20, 2017
Publication date	Sep 5, 2023
Grant date	Sep 5, 2023

Abstract

Methods for treating AL amyloidosis using chimeric antigen receptors targeting CS1 are described.

First claim

What is claimed is:

1. A method for treating light chain amyloidosis comprising administering to a patient in need thereof a population of human T cells expressing a chimeric antigen receptor, wherein chimeric antigen receptor comprises an amino acid sequence selected from: SEQ ID NOs: 30, 31, 33, 34, 36, 37, 39, 40, 42, 43, 45, and 46.

2. The method of claim 1 , wherein the chimeric antigen receptor consists of an amino acid sequence identical to an amino acid sequence selected from: SEQ ID NOs: 30, 31, 33, 34, 36, 37, 39, 40, 42, 43, 45, and 46.

3. The method of claim 1 , wherein at least 20%, 30%, or 40% of the transduced human T cells are central memory T cells.

4. The method of claim 1 , wherein at least 30% of the transduced human T cells are CD4+ and CD62L+ or CD8+ and CD62L+.

5. The method of claim 1 , wherein the population of human T cells are autologous to the patient.

6. The method of claim 1 , wherein the population of human T cells are allogenic to the patient.

7. A method for treating light chain amyloidosis comprising administering to a patient in need thereof a population of human T cells expressing transduced by a vector comprising an expression cassette encoding a chimeric antigen receptor, wherein chimeric antigen receptor comprises:
(a) a CS1 scFv comprising SEQ ID NO: 1; a spacer domain comprising SEQ ID NO: 9; a transmembrane domain comprising SEQ ID NO: 15; a co-signaling domain comprising SEQ ID NO: 23; and a CD3 ζ signaling domain comprising SEQ ID NO: 21;
(b) a CS1 scFv comprising SEQ ID NO: 1; a spacer domain comprising SEQ ID NO: 9; a transmembrane domain comprising SEQ ID NO: 16; a co-signaling domain comprising SEQ ID NO: 24; and a CD3 ζ signaling domain comprising SEQ ID NO: 21;
(c) a CS1 scFv comprising SEQ ID NO: 1; a spacer domain comprising SEQ ID NO: 11; a transmembrane domain comprising SEQ ID NO: 16; a co-signaling domain comprising SEQ ID NO: 24; and a CD3 ζ signaling domain comprising SEQ ID NO: 21;
(d) a CS1 scFv comprising SEQ ID NO: 1; a spacer domain comprising SEQ ID NO: 11; a transmembrane domain comprising SEQ ID NO: 15; a co-signaling domain comprising SEQ ID NO: 23; and a CD3 ζ signaling domain comprising SEQ ID NO: 21;
(e) a CS1 scFv comprising SEQ ID NO: 1; a spacer domain comprising SEQ ID NO: 2; a transmembrane domain comprising SEQ ID NO: 16; a co-signaling domain comprising SEQ ID NO: 24; and a CD3 ζ signaling domain comprising SEQ ID NO: 21; and
(f) a CS1 scFv comprising SEQ ID NO: 1; a spacer domain comprising SEQ ID NO: 2; a transmembrane domain comprising SEQ ID NO: 15; a co-signaling domain comprising SEQ ID NO: 23; and a CD3 ζ signaling domain comprising SEQ ID NO: 21.

8. The method of claim 7 , wherein the chimeric antigen receptor comprises an amino acid sequence selected from any one of SEQ ID NOs: 30, 31, 33, 34, 36, 37, 39, 40, 42, 43, 45, and 46.

9. The method of claim 7 , wherein at least 30% of the transduced human T cells are CD4+ and CD62L+ or CD8+ and CD62L+.

10. The method of claim 7 , wherein the population of human T cells are autologous to the patient.

11. The method of claim 7 , wherein the population of human T cells are allogenic to the patient.

Assignees

• Hope City

Inventors

• Wang Xiuli
• Forman Stephen J

Classifications

• A61K40/4224

  Molecules with a "CD" designation not provided for elsewhere · 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

• A61K2239/38

  characterised by the dose, timing or administration schedule · CPC title

• A61K2239/31

  characterized by the route of administration · CPC title