Yeda Research and Develpment & Co. Ltd

Other

Tel Hashomer Medical Research Infrastructure and Services Ltd.

Yeda Research and Devolpment Co. Ltd.

Yair Reisner

Esther Bachar-Lustig

Noga Or-Geva

Eran Ophir

Yaki Eidelstein

Elias Shezen

Assaf Lask

Rotem Gidron Budovsky

Anna Aronovich

Benjamin Dekel

Smadar Eventov-Friedman

Helena Katchman

Dalit Tchorsh

Ran Afik

Shlomo Dagan

Sivan Kagan

Massimo Martelli

Shlomit Reich-Zeliger

Chava Rosen

Esther Aboud-Pirak

Gideon Rechavi

Adva Cohen

George Lowell

Irit Milman Krentsis

Dalit Tchorsh-Yutsis

Carmit Hillel-karniel

A method of generating an isolated population of non graft versus host disease (GvHD) inducing cells comprising a central memory T-lymphocyte (Tcm) phenotype, the cells being tolerance inducing cells and/or endowed with anti-disease activity, and capable of homing to the lymph nodes following transplantation is disclosed. The method comprising: (a) providing a population of at least 70% memory T cells; (b) contacting the population of memory T cells with an antigen or antigens so as to allow enrichment of antigen reactive cells; and (c) culturing the cells resulting from step (b) in the presence of cytokines so as to allow proliferation of cells comprising the Tcm phenotype. Cells generated by the method, pharmaceutical compositions and methods of treatment are also disclosed.

Veto cells generated from memory T cells

An isolated cytotoxic T-lymphocyte (CTL), said CTL being a tolerance inducing cell and substantially depleted of alloreactivity, and wherein said CTL does not comprise a central memory T-lymphocyte (Tcm) phenotype, the CTL being transduced to express a cell surface receptor comprising a T cell receptor signaling module, is disclosed. Methods of generating same and using same are also disclosed.

Genetically modified veto cells and use of same in immunotherapy

A method of treating a subject in need of a non-syngeneic cell or tissue graft is disclosed. The method comprising: (a) transplanting into a subject a dose of T cell depleted immature hematopoietic cells, wherein the T cell depleted immature hematopoietic cells comprise less than 5&#xd7;10CD3+ T cells per kilogram body weight of the subject, and wherein the dose comprises at least about 5&#xd7;CD34+ cells per kilogram body weight of the subject, and wherein the T cell depleted immature hematopoietic cells are obtained by separating the T cells from the immature hematopoietic cells by magnetic cell sorting, and (b) administering to the subject a therapeutically effective amount of cyclophosphamide, wherein the therapeutically effective amount comprises 25-200 mg per body weight, thereby treating the subject.

Combination therapy for a stable and long term engraftment using specific protocols for T/B cell depletion

A method of treating a subject in need of a non-syngeneic cell or tissue graft is disclosed. The method comprising: (a) transplanting into a subject a dose of T cell depleted immature hematopoietic cells, wherein the T cell depleted immature hematopoietic cells comprise less than 5&#xd7;10CD3T cells per kilogram body weight of the subject, and wherein the dose comprises at least about 5&#xd7;10CD34+ cells per kilogram body weight of the subject; and subsequently (b) administering to the subject a therapeutically effective amount of cyclophosphamide, wherein the therapeutically effective amount comprises 25-200 mg per kilogram body weight, thereby treating the subject.

Combination therapy for a stable and long term engraftment

A method of generating an isolated population of cells comprising anti-third party cells having a central memory T-lymphocyte (Tcm) phenotype, the cells being tolerance-inducing cells and/or endowed with anti-disease activity, and capable of homing to the lymph nodes following transplantation is disclosed. The method comprising: (a) contacting peripheral blood mononuclear cells (PBMC) with a third party antigen or antigens in the presence of IL-21 so as to allow enrichment of antigen reactive cells; and (b) culturing the cells resulting from step (a) in the presence of IL-21, IL-15 and IL-7 in an antigen free environment so as to allow proliferation of cells comprising the central memory T-lymphocyte (Tcm) phenotype.

Anti third party central memory T cells, methods of producing same and use of same in transplantation and disease treatment

An isolated cell having a central memory T-lymphocyte (Tcm) phenotype, the cell being tolerance-inducing cell and capable of homing to the lymph nodes following transplantation, the cell being transduced to express a cell surface receptor comprising a T cell receptor signaling module is disclosed. Methods of generating same and using same are also disclosed.

Genetically modified anti-third party central memory T cells and use of same in immunotherapy

A method of transplantation is disclosed. The method comprising administering to a subject in need of transplantation of cells in suspension, a therapeutically effective amount of anti-third party cells having a central memory T-lymphocyte (Tcm) phenotype, said anti-third party cells being tolerance-inducing cells and capable of homing to the lymph nodes following transplantation, wherein said cells in suspension comprise non-hematopoietic cells or hematopoietic cells which are not stem cells. Methods of treating and kits are also provided.

Methods of transplantation and disease treatment

A method of transplantation is disclosed. The method comprising administering to a subject in need of transplantation of cells in suspension, a therapeutically effective amount of tolerance inducing anti-third party cytotoxic T-lymphocytes (CTLs), wherein the tolerance inducing anti-third party CTLs are generated by directing T-lymphocytes of a donor against a third party antigen or antigens, the tolerance inducing anti-third party CTLs being substantially depleted of T-lymphocytes capable of developing into alloreactive CTLs, and wherein the tolerance inducing anti-third party CTLs do not comprise cells having a central memory T-lymphocyte (Tcm) phenotype, wherein the cells in suspension comprise non-hematopoietic cells or hematopoietic cells which are not stem cells. Methods of treating and kits are also provided.

A method of conditioning a subject in need of transplantation of progenitor cells in suspension of a tissue of interest is disclosed. The method comprising: (a) administering to a subject a therapeutically effective amount of an agent capable of inducing damage to the tissue of interest, wherein the damage results in proliferation of resident stem cells in the tissue; and subsequently (b) subjecting the subject to an agent which ablates the resident stem cells in the tissue. A method of transplanting progenitor cells in suspension of a tissue of interest to a subject in need thereof is also disclosed.

Conditioning protocols and use of same for tissue regeneration

A method of treating a subject in need of a non-syngeneic cell or tissue graft is disclosed. The method comprising: (a) transplanting into a subject a dose of T cell depleted immature hematopoetic cells, wherein the T cell depleted immature hematopoetic cells comprise less than 5&#xd7;105 CD3+ T cells per kilogram body weight of the subject, and wherein the dose comprises at least about 5&#xd7;106 CD34+ cells per kilogram body weight of the subject, and wherein the T cell depleted immature hematopoetic cells are obtained by separating the T cells from the immature hematopoetic cells by magnetic cell sorting, and (b) administering to the subject a therapeutically effective amount of cyclophosphamide, wherein the therapeutically effective amount comprises 25-200 mg per body weight, thereby treating the subject.

A pharmaceutical composition comprising as an active ingredient an isolated population of cell suspension from a mammalian fetal pulmonary tissue is disclosed. The fetal pulmonary tissue is at a developmental stage corresponding to that of a human pulmonary organ/tissue at a gestational stage selected from a range of about 20 to about 22 weeks of gestation. Methods of using the pharmaceutical composition are also disclosed.

Mammalian fetal pulmonary cells and therapeutic use of same

An isolated population of cells comprising non-GVHD inducing anti-third party cells having a central memory T-lymphocyte (Tcm) phenotype is provided. The cells being tolerance-inducing cells and capable of homing to the lymph nodes following transplantation. Methods of generating same, use of same and methods of treatment are also provided.

Methods of modulating mobilization of cells from the bone marrow are provided. In a specific embodiment there is provided a method of increasing mobilization of hematopoietic precursors from the bone marrow to the peripheral blood in a subject in need thereof, the method comprising: (a) administering to the subject an agent which downregulates an activity or expression of a coagulation factor or an effector thereof; and (b) harvesting the hematopoietic precursors from the peripheral blood.

Growing community of inventors

Old Jaffa, Israel

Yair Reisner