Compositions and methods for immunotherapy
AssigneeMemorial Sloan Kettering Cancer Center
InventorsVictor D. Fedorov, Michel Sadelain
Life of this patent
Estimating the term…
Abstract
The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing an antigen recognizing receptor and an inhibitory chimeric antigen receptor (iCAR). Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.
Claims18
A T cell comprising:
- a) a chimeric antigen receptor (CAR) comprising an extracellular antigen-binding domain comprising a single chain variable fragment (scFv) that binds to a first antigen that is expressed at the surface of a tumor cell, and an intracellular signaling domain that is capable of activating the T cell and comprises a signaling domain of CD28, and
- b) an inhibitory chimeric antigen receptor (iCAR) comprising an extracellular antigen-binding domain comprising a single chain variable fragment (scFv) that binds to a second antigen that is not expressed on the tumor cell surface, and a signaling domain of an immunoinhibitory receptor selected from the group consisting of CTLA-4, PD-1, LAG-3, 2B4, and BTLA,
- wherein binding of the CAR to the first antigen induces cytotoxicity of the T cell, an binding of the iCAR to the second antigen reduces the cytotoxicity of the T cell induced by the CAR.
A pharmaceutical composition comprising a pharmaceutically acceptable excipient and an effective amount of T cells, wherein said T cell comprises:
- (a) a chimeric antigen receptor (CAR) comprising an extracellular antigen-binding domain comprising a single chain variable fragment (scFv) that binds to a first antigen that is expressed at the surface of a tumor cell, and an intracellular signaling domain that is capable of activating the T cell and comprises a signaling domain of CD28, and
- (b) an inhibitory chimeric antigen receptor (iCAR) comprising an extracellular antigen-binding domain comprising a single chain variable fragment (scFv) that binds to a second antigen that is not expressed on the tumor cell surface, and a signaling domain of an immunoinhibitory receptor selected from the group consisting of CTLA-4, PD-1, LAG-3, 2B4, and BTLA, wherein binding of the CAR to the first antigen induces cytotoxicity of the T cell, and binding of the iCAR to the second antigen reduces the cytotoxicity of the T cell induced by the CAR.
A kit comprising a T cell, wherein said T cells comprises:
- (a) a chimeric antigen receptor (CAR) comprising an extracellular antigen-binding domain comprising a single chain variable fragment (scFv) that binds to a first antigen that is expressed at the surface of a tumor cell, and an intracellular signaling domain that is capable of activating the T cell and comprises a signaling domain of CD28, and
- (b) an inhibitory chimeric antigen receptor (iCAR) comprising an extracellular antigen-binding domain comprising a single chain variable fragment (scFv) that binds to a second antigen that is not expressed on the tumor cell surface, and a signaling domain of an immunoinhibitory receptor selected from the group consisting of CTLA-4, PD-1, LAG-3, 2B4, and BTLA,
- wherein binding of the CAR to the first antigen induces cytotoxicity of the T cell, and binding of the iCAR to the second antigen reduces the cytotoxicity of the T cell induced by the CAR.
Dependencies are inferred from the claim text.