Engineering of gamma delta t cells and compositions thereof
AssigneeGammaDelta Therapeutics Ltd
InventorIstvan KOVACS
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Abstract
The present invention provides methods of engineering γδ T cells (e.g., vδ1 T cells and vδ2 T cells) by transduction with a viral vector (e.g., a viral vector with a betaretroviral pseudotype and a 5 Retroviridae family viral vector backbone). Further provided are compositions of engineered γδ T cells and methods of using the same.
Claims119
A method of producing a population of engineered γδ T cells, the method comprising transducing a population of γδ T cells with a viral vector comprising a betaretroviral pseudotype and a Retroviridae family viral vector backbone.
A method of producing a population of engineered γδ T cells, the method comprising:
- (i) providing a starting population of γδ T cells;
- (ii) culturing the starting population of γδ T cells for a first culture period in the absence of a viral vector to produce a population of primed γδ T cells;
- and
- (iii) culturing the population of primed γδ T cells for a second culture period in the presence of a viral vector comprising a betaretroviral pseudotype in an amount effective to transduce at least 3% of the primed γδ T cells, thereby producing the population of engineered γδ T cells.
A method of producing a population of engineered γδ T cells, the method comprising:
- (i) providing a starting population of γδ T cells;
- and
- (ii) culturing the starting population of γδ T cells in the presence of IL-15 and a viral vector comprising a betaretroviral pseudotype in an amount effective to transduce at least 3% of the starting population of γδ T cells, thereby producing the population of engineered γδ T cells.
A method of producing a population of γδ T cells expressing a CAR, the method comprising transducing a population of γδ T cells with a viral vector comprising:
- (i) a transgene encoding the CAR;
- (ii) a betaretroviral pseudotype;
- and
- (iii) a Retroviridae family viral vector backbone.
A method of producing a population of γδ T cells expressing a CAR and an armor protein, the method comprising transducing a population of γδ T cells with a viral vector comprising:
- (i) a first transgene encoding the CAR;
- (ii) a second transgene encoding the armor protein;
- (iii) a betaretroviral pseudotype;
- and
- (iv) a Retroviridae family viral vector backbone.
A method of producing a population of γδ T cells expressing a CAR, the method comprising:
- (i) providing a starting population of γδ T cells;
- (ii) culturing the starting population of γδ T cells for a first culture period in the absence of a viral vector to produce a population of primed γδ T cells;
- and
- (iii) culturing the population of primed γδ T cells for a second culture period in the presence of a viral vector comprising a betaretroviral pseudotype and a transgene encoding the CAR, wherein the viral vector is in an amount effective to transduce at least 3% of the primed γδ T cells, thereby producing the population of γδ T cells expressing the CAR.
A method of producing a population of γδ T cells expressing a CAR and an armor protein, the method comprising:
- (i) providing a starting population of γδ T cells;
- (ii) culturing the starting population of γδ T cells for a first culture period in the absence of a viral vector to produce a population of primed γδ T cells;
- and
- (iii) culturing the population of primed γδ T cells for a second culture period in the presence of a viral vector comprising a betaretroviral pseudotype, a first transgene encoding the CAR, and a second transgene encoding the armor protein, wherein the viral vector is in an amount effective to transduce at least 3% of the primed γδ T cells, thereby producing the population of γδ T cells expressing the CAR and the armor protein.
A method of producing a population of γδ T cells expressing a CAR, the method comprising:
- (i) providing a starting population of γδ T cells;
- and
- (ii) culturing the starting population of γδ T cells in the presence of IL-15 and a viral vector comprising a betaretroviral pseudotype and a transgene encoding the CAR, wherein the viral vector is in an amount effective to transduce at least 3% of the starting population of γδ T cells, thereby producing the population of engineered γδ T cells expressing the CAR.
A method of producing a population of γδ T cells expressing a CAR and an armor protein, the method comprising:
- (i) providing a starting population of γδ T cells;
- and
- (ii) culturing the starting population of γδ T cells in the presence of IL-15 and a viral vector comprising a betaretroviral pseudotype, a first transgene encoding the CAR, and a second transgene encoding the armor protein, wherein the viral vector is in an amount effective to transduce at least 3% of the starting population of γδ T cells, thereby producing the population of engineered γδ T cells expressing the CAR and the armor protein.
Dependencies are inferred from the claim text.