Cell compositions and methods for cancer therapy

Patent metadata

Field	Value
Publication number	US-10344073-B2
Application number	US-201515110111-A
Country	US
Kind code	B2
Filing date	Jan 8, 2015
Priority date	Jan 9, 2014
Publication date	Jul 9, 2019
Grant date	Jul 9, 2019

Abstract

Provided is directed to the field of immunotherapy. Specifically, provided are compositions and methods for improved T cell modulation ex vivo and in vivo and for the treatment of cancer and other pathologies. More specifically, embodiments of the subject matter are directed to the use of soluble NTB-A polypeptides or agonists thereof for the treatment of cancer patients, for preventing and treating cytopenia in susceptible patients, and for the ex vivo preparation of improved cell compositions.

First claim

The invention claimed is:

1. A method for preparing a cell composition for adoptive transfer immunotherapy, comprising incubating tumor infiltrating lymphocytes ex vivo with an isolated NTB-A ectodomain in the presence of an anti-CD3 antibody and allogeneic feeder cells for 8 to 15 days, in an amount and under conditions effective to reduce activation-induced T cell death without the addition of exogenous IL-2.

2. The method of claim 1 , wherein the isolated NTB-A ectodomain further comprises an epitope tag.

3. The method of claim 1 , wherein the incubation with the NTB-A ectodomain is performed so as to up-regulate CD137 expression on T cells.

4. A cell composition for adoptive transfer immunotherapy, prepared by a method comprising: incubating tumor infiltrating lymphocytes ex vivo with an isolated NTB-A ectodomain in the presence of an anti-CD3 antibody and allogeneic feeder cells, for 8 to 15 days in an amount and under conditions effective to reduce activation-induced T cell death without the addition of exogenous IL-2.

5. The cell composition of claim 4 , wherein the isolated NTB-A ectodomain further comprises an epitope tag.

6. The cell composition of claim 4 , wherein the incubation with the NTB-A ectodomain is performed so as to up-regulate CD137 expression on T cells.

7. The cell composition of claim 4 , wherein said feeder cells are attenuated peripheral blood mononuclear cells, and wherein the incubation with the NTB-A ectodomain is performed for 8 to 15 days at a ratio of T cells to feeder cells of 1:200 to 1:100.

8. The cell composition of claim 7 , wherein said incubation is performed so as to increase cytotoxic T cell activity while minimizing regulatory T cell activity.

9. The cell composition of claim 7 , wherein said incubation is performed to thereby improve cytotoxic T cell activity and survivability beyond the levels achieved by incubation with exogenous IL-2.

Assignees

• Hadasit Med Res Service

Inventors

• Rutenberg Abraham
• Uzana Ronny
• Lotem Michal
• Machlenkin Arthur
• Eisenberg Galit
• Peretz-Yablonsky Tamar
• Frankenburg Shoshana
• Engelstein Roni

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07K16/2803

  against the immunoglobulin superfamily · CPC title

• C12N2501/998

  Proteins not provided for elsewhere · CPC title

• C07K2317/75

  Agonist effect on antigen · CPC title

• A61K2039/505

  comprising antibodies · CPC title