Targeted chimeric antigen receptor modified T cells for treatment of IL13Rα2 positive malignancies

Patent metadata

Field	Value
Publication number	US-12419954-B2
Application number	US-202117796349-A
Country	US
Kind code	B2
Filing date	Jan 19, 2021
Priority date	Jan 31, 2020
Publication date	Sep 23, 2025
Grant date	Sep 23, 2025

Abstract

Chimeric antigen receptor molecules that include a variant IL-13. The variant IL-13 are more selective for IL13Rα2 than IL13Rα1 by virtue of weaker binding to IL13Rα1. The chimeric antigen receptors can be used to treat IL13Rα2 expressing cancers.

First claim

What is claimed is:

1. A nucleic molecule comprising a nucleotide sequence encoding a chimeric antigen receptor (CAR), wherein—the CAR comprises or consists of an amino acid sequence selected from the group consisting of an amino acid sequence that is at least 98% identical to an amino acid sequence selected from SEQ ID NOs: 29, 30, 32, 33, 35, 36, 38 and 39 and comprises a targeting domain comprising or consisting of an amino acid sequence identical to SEQ ID NO: 26 or 27.

2. The nucleic acid molecule of claim 1 , wherein the chimeric antigen receptor comprises or consists of an amino acid sequence selected from the group consisting of an amino acid sequence selected from SEQ ID NOs: 29, 30, 32, 33, 35, 36, 38 and 39.

3. The nucleic acid molecule of claim 1 , wherein the chimeric antigen receptor comprises or consists of an amino acid sequence selected from the group consisting of: an amino acid sequence selected from SEQ ID NOs: 29, 32, 35 and 38.

4. An expression vector comprising the nucleic acid molecule of claim 1 .

5. A viral vector comprising the nucleic acid molecule of claim 1 .

6. A population of human T cells transduced by a vector comprising the nucleic acid molecule of claim 1 .

7. The population of human T cells of claim 6 , wherein the population of human T cells comprise central memory T cells, naive memory T cells, pan T cells, or PBMC depleted for CD25+ cells and CD14+ cells.

8. A method of preparing CAR T cells comprising: providing a population of autologous or allogeneic human T cells and transducing the T cells by a vector comprising the nucleic acid molecule of claim 1 .

9. A method of treating a cancer patient suffering from a cancer expressing IL-13Rα2, wherein the cancer is selected from glioblastoma, pancreatic ductal adenocarcinoma, melanoma, ovarian carcinoma, renal cell carcinoma, breast cancer or lung cancer, comprising administering a population of autologous or allogeneic human T cells transduced by a vector comprising the nucleic acid molecule of claim 1 .

10. The method of claim 9 , wherein the cells are administered locally or systemically.

11. The method of claim 10 , wherein the cells are administered by single or repeat dosing.

12. The method of claim 9 , wherein the patient is suffering from glioblastoma.

13. The method of claim 12 , wherein the chimeric antigen receptor comprises or consists of an amino acid sequence selected from the group consisting of an amino acid sequence selected from SEQ ID NOs: 29, 30, 32, 33, 35, 36, 38 and 39.

14. The method of claim 13 , wherein the population of human T cells are allogenic human T cells.

15. The method of claim 13 , wherein the population of human T cells are autologous human T cells.

16. A chimeric antigen receptor comprising or consisting of an amino acid sequence selected from the group consisting of an amino acid sequence that is at least 98% identical to an amino acid sequence selected from SEQ ID NOs: 29, 30, 32, 33, 35, 36, 38 and 39.

17. The chimeric antigen receptor of claim 16 , comprising or consisting of an amino acid sequence selected from the group consisting of an amino acid sequence selected from SEQ ID NOs: 29, 30, 32, 33, 35, 36, 38 and 39.

18. The chimeric antigen receptor of claim 16 , comprising or consisting of an amino acid sequence selected from the group consisting of an amino acid sequence selected from SEQ ID NOs: SEQ ID NOs: 29, 32, 35 and 38.

19. A population of human T cells expressing the chimeric antigen receptor of claim 16 .

20. The population of human T cells of claim 19 , wherein the population of human T cells comprise central memory T cells, naive memory T cells, pan T cells, or PBMC depleted for CD25+ cells and CD14+ cells.

Assignees

• Hope City
• Univ Leland Stanford Junior

Inventors

• Brown Christine E
• Stern Lawrence
• Yang Xin
• Garcia K Christopher
• Gonzalez Ignacio Moraga

Classifications

• A61K40/4217

  Receptors for interleukins [IL] · CPC title

• A61K40/11

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

• A61K2239/47

  Brain; Nervous system · CPC title

• A61K2239/31

  characterized by the route of administration · CPC title

• A61K2239/38

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