Cell compositions and methods for cancer therapy

• US 10,344,073 B2
• Filed: 01/08/2015
• Issued: 07/09/2019
• Est. Priority Date: 01/09/2014
• Status: Active Grant

• Current Assignee: Hadasit Medical Research Services & Development Ltd (Hadassah, The Women's Zionist Organization of America, Inc.)
• Original Assignee: Hadasit Medical Research Services & Development Ltd (Hadassah, The Women's Zionist Organization of America, Inc.)
• Inventors: Rutenberg, Abraham, Uzana, Ronny, Lotem, Michal, Machlenkin, Arthur, Eisenberg, Galit, Peretz-Yablonsky, Tamar, Frankenburg, Shoshana, Engelstein, Roni
• Primary Examiner(s): Sang, Hong
• Application Number:
  US15/110,111
• Publication Number:
  US 20160333072A1
• Time in Patent Office: 1,643 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/876 Skin, melanoma
• CPC Class Codes: A61K 2239/57 Skin; melanoma
• CPC Class Codes: A61K 35/17 Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes when activated by a specific antigen A61K39/00
• CPC Class Codes: A61K 38/1774 Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/464491 Melan-A/MART
• CPC Class Codes: A61K 39/464492 Glycoprotein 100 [Gp100]
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/70503 Immunoglobulin superfamily
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 2317/75 Agonist effect on antigen
• CPC Class Codes: C12N 2501/2302 Interleukin-2 (IL-2)
• CPC Class Codes: C12N 2501/998 Proteins not provided for elsewhere
• CPC Class Codes: C12N 5/0638 Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]

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.

Claims

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.