Immune cells defective for SUV39H1

Patent metadata

Field	Value
Publication number	US-10576103-B2
Application number	US-201916425008-A
Country	US
Kind code	B2
Filing date	May 29, 2019
Priority date	Jun 20, 2017
Publication date	Mar 3, 2020
Grant date	Mar 3, 2020

Abstract

The present invention relates to an engineered immune cell defective for Suv39h1. Preferably, said engineered immune cell further comprises a genetically engineered antigen receptor that specifically binds a target antigen. The present invention also relates to a method for obtaining a genetically engineered immune cell comprising a step consisting in inhibiting the expression and/or activity of Suv39h1 in the immune cell; and further optionally comprising a step consisting in introducing in the said immune cell a genetically engineered antigen receptor that specifically binds to a target antigen. The invention also encompasses said engineered immune cell for their use in adoptive therapy, notably for the treatment of cancer.

First claim

The invention claimed is:

1. A method for treating a subject suffering from cancer comprising:
administering to said subject an engineered immune cell, wherein the immune cell is a T cell, NK cell or T cell progenitor, comprising a genetically engineered antigen receptor and an inactivated or disrupted SUV39H1 gene, wherein inactivation or disruption of the SUV39H1 gene results in enhanced anti-cancer activity of said immune cell.

2. The method of claim 1 , wherein the engineered immune cell is a T cell or T cell progenitor.

3. The method of claim 1 , wherein the immune cell is a CD4+ T cell, or a CD8+ T cell, or a CD4+ and CD8+ T cell.

4. The method of claim 1 wherein the cell comprises a second genetically engineered antigen receptor that recognizes a different antigen.

5. The method of claim 1 , wherein the genetically engineered antigen receptor is a T cell receptor (TCR).

6. The method of claim 2 , wherein the genetically engineered antigen receptor is a T cell receptor (TCR).

7. The method of claim 1 , wherein the genetically engineered antigen receptor is a chimeric antigen receptor (CAR).

8. The method of claim 2 , wherein the genetically engineered antigen receptor is a chimeric antigen receptor (CAR).

9. The method of claim 1 , wherein the genetically engineered antigen receptor is a CAR comprising (a) an intracellular signaling domain from CD3 zeta chain and (b) one or more costimulatory domains of 4-1BB, CD28, ICOS, OX40 or DAP10.

10. The method of claim 2 , wherein the genetically engineered antigen receptor is a CAR comprising (a) an intracellular signaling domain from CD3 zeta chain and (b) one or more costimulatory domains of 4-1BB, CD28, ICOS, OX40 or DAP10.

11. The method of claim 1 , wherein the engineered immune cell is autologous.

12. The method of claim 1 , wherein the engineered immune cell is allogeneic.

13. A method for treating a subject suffering from cancer comprising administering to said subject:
(1) an engineered immune cell, wherein the immune cell is a T cell, NK cell or T cell progenitor, comprising a genetically engineered antigen receptor and an inactivated or disrupted SUV39H1 gene, wherein inactivation or disruption of the SUV39H1 gene results in enhanced anti-cancer activity of said immune cell; and
(2) a second cancer therapeutic agent.

14. The method of claim 13 , wherein the second cancer therapeutic agent is an immune checkpoint modulator, cancer vaccine, chemotherapeutic or anti-angiogen.

15. A method for treating a subject suffering from cancer comprising administering to said subject:
(1) an engineered immune cell, wherein the immune cell is a T cell, NK cell or T cell progenitor, comprising a genetically engineered antigen receptor and an inactivated or disrupted SUV39H1 gene, wherein inactivation or disruption of the SUV39H1 gene results in enhanced anti-cancer activity of said immune cell; and
(2) an immune checkpoint modulator.

16. The method of claim 15 wherein the immune checkpoint modulator is an inhibitor of PD1, CTLA4, LAG3, BTLA, OX2R, TIM-3, TIGIT, LAIR-1, PGE2 receptor, EP2/4 adenosine receptor, or A2AR.

17. The method of claim 15 wherein the immune checkpoint modulator is an anti-PD-1 inhibitor or anti-PDL-1 inhibitor.

18. The method of claim 1 , wherein the disrupted SUV39H1 gene comprises a deletion.

Assignees

• Inst Curie
• Institut National De La Sante Et Da La Rech Medicale Inserm
• Centre Nat Rech Scient
• Institut National De La Sante Et De La Rech Medicals Inserm

Inventors

• Amigorena Sebastian
• Piaggio Eliane
• Goudot Christel
• Pace Luigia
• Almouzni Genevieve

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C12N2510/00

  Genetically modified cells · CPC title

• C07K14/7051

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

• C07K14/70521 Primary

  CD28, CD152 · CPC title