Improved cell compositions and methods for cancer therapy

Patent metadata

Field	Value
Publication number	US-2016333072-A1
Application number	US-201515110111-A
Country	US
Kind code	A1
Filing date	Jan 8, 2015
Priority date	Jan 9, 2014
Publication date	Nov 17, 2016
Grant date	—

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

1 .- 44 . (canceled)

45 . A method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an isolated NTB-A ectodomain or an agonist thereof, wherein said subject is afflicted with a tumor selected from the group consisting of: a tumor characterized by lack of substantial NTB-A surface expression, a solid tumor and a tumor characterized by surface expression of CD137.

46 . The method of claim 45 , wherein the NTB-A ectodomain is human NTB-A ectodomain.

47 . The method of claim 45 , wherein the NTB-A ectodomain further comprises an epitope tag and/or a serum half-life elongating substance, or wherein the agonist is an antibody specific to an NTB-A ectodomain.

48 . The method of claim 45 , wherein said subject is a cytopenic subject, or a subject at risk of developing cytopenia.

49 . The method of claim 45 , wherein IL-2 is not exogenously administered to said subject, or further comprising administering to said subject a CD137 ligand or an agonist thereof.

50 . A method of reducing or inhibiting T cell death or for treating or preventing cytopenia, comprising contacting T cells with an effective amount of an isolated NTB-A ectodomain or an agonist thereof.

51 . The method of claim 50 for reducing or inhibiting T cell death, wherein the contacting is performed in vitro.

52 . The method of claim 50 for reducing or inhibiting T cell death in a subject suffering from or at risk of developing cytopenia, wherein the contacting is performed in vivo.

53 . The method of claim 50 wherein the agonist is an antibody specific to human NTB-A ectodomain.

54 . The method of claim 50 for treating or preventing cytopenia in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an isolated NTB-A ectodomain or an agonist thereof, thereby treating or preventing cytopenia in said subject.

55 . The method of claim 54 , wherein the cytopenia is associated with radiation or chemotherapy, or for the treatment or prevention of lymphocytopenia.

56 . The method of claim 54 wherein said subject is not afflicted with X-linked lymphoproliferative disease (XLP).

57 . The method of claim 54 wherein said subject is not afflicted with cancer.

58 . A method for preparing a cell composition, comprising incubating a T cell containing cell population ex vivo with an effective amount of an isolated NTB-A ectodomain or an agonist thereof, and further comprising providing the cell population with a T cell receptor (TCR) stimulation.

59 . The method of claim 58 , wherein the T cell containing cell population is incubated with the isolated NTB-A ectodomain or agonist thereof in the presence TCR stimulation and feeder cells and without the addition of exogenous IL-2.

60 . The method of claim 58 , wherein the composition is adapted for adoptive transfer immunotherapy, or wherein the incubation is performed in the presence of exogenous CD137 ligand or an agonist thereof, or wherein the population comprises CD8 + T cells.

61 . The method of claim 58 , wherein the incubation with the NTB-A ectodomain or agonist is performed so as to up-regulate CD137 expression on T cells, or wherein the incubation with the NTB-A ectodomain or agonist is performed so as to enhance the number of T cells by at least 100-fold.

62 . A cell composition prepared by the method of claim 58 .

63 . A method of treating cancer in a subject in need thereof, comprising administering to the subject a cell composition according to claim 62 , thereby treating cancer in said subject, wherein said T cell containing population is obtained from the subject, or from a donor substantially histocompatible with said subject.

64 . The method of claim 63 , wherein the NTB-A ectodomain is human NTB-A ectodomain, or wherein the agonist is an antibody specific to an NTB-A ectodomain.

65 . The method of claim 63 , further comprising administering an effective amount of an isolated NTB-A ectodomain or an agonist thereof to said subject, or wherein IL-2 is not exogenously administered to said subject.

66 . The method of claim 63 , wherein said subject is afflicted with a tumor characterized by lack of substantial NTB-A surface expression or with a tumor characterized by surface expression of CD137, or
wherein said subject is a cytopenic subject, or a subject at risk of developing cytopenia.

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

• C12N2501/998

  Proteins not provided for elsewhere · CPC title

• A61K45/06

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

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title

• A61K2039/505

  comprising antibodies · CPC title