Genetically modified anti-third party central memory T cells and use of same in immunotherapy
AssigneeYeda Research and Development Co. Ltd.
InventorsYair Reisner, Noga Or-Geva, Eran Ophir, Yaki Eidelstein, Rotem Gidron Budovsky
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Abstract
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.
Claims18
A method of generating an isolated cell having a central memory T-lymphocyte (Tcm) phenotype and expressing a cell surface receptor comprising a heterologous T cell receptor signaling module, said cell being tolerance-inducing cell and capable of homing to the lymph nodes following transplantation, the method comprising transducing a cell having a Tcm phenotype with a polynucleotide encoding a cell surface receptor comprising a T cell receptor signaling module and an extracellular domain directed against a disease antigen, wherein said cell having said Tcm phenotype is generated by a 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 said cells resulting from step (a) in the presence of IL-21, IL-15 and IL-7 so as to allow proliferation of anti-third party cells comprising said Tcm phenotype.
A method of generating an isolated cell having a central memory T-lymphocyte (Tcm) phenotype and expressing a chimeric antigen receptor (CAR), said cell being tolerance-inducing cell and capable of homing to the lymph nodes following transplantation, the method comprising transducing a cell having a Tcm phenotype with a polynucleotide encoding a chimeric antigen receptor (CAR) comprising an extracellular domain directed against a disease antigen, wherein said cell having said Tcm phenotype is generated by a 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 said cells resulting from step (a) in the presence of IL-21, IL-15 and IL-7 so as to allow proliferation of anti-third party cells comprising said Tcm phenotype.
Dependencies are inferred from the claim text.