Use of icos-based cars to enhance antitumor activity and car persistence
AssigneeThe Trustees of the University of Pennsylvania
InventorsCarl H. June, Sonia Guedan Carrio, Yangbing Zhao, John Scholler
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Abstract
The present invention provides compositions and methods for treating cancer in a human. The invention includes administering a genetically modified Th17 cell to express a CAR having an antigen binding domain, a transmembrane domain, and an ICOS intracellular signaling domain.
Claims43
1-44. (canceled)
A method for stimulating a T cell-mediated immune response to a target cell population or tissue in a mammal, the method comprising administering to the mammal an effective amount of a cell genetically modified to express a CAR, wherein the CAR comprises an antigen binding domain, an ICOS transmembrane domain, and an ICOS intracellular signaling domain, wherein the ICOS transmembrane domain comprises the amino acid sequence of SEQ ID NO:
- 12.
A method of providing an anti-tumor immunity in a mammal, the method comprising administering to the mammal an effective amount of a cell genetically modified to express a CAR, wherein the CAR comprises an antigen binding domain, an ICOS transmembrane domain, and an ICOS intracellular signaling domain, thereby providing an anti-tumor immunity in the mammal, wherein the ICOS transmembrane domain comprises the amino acid sequence of SEQ ID NO:
- 12.
A method of treating a mammal having a disease, disorder or condition associated with an elevated expression of a tumor antigen, the method comprising administering to the mammal an effective amount of a cell genetically modified to express a CAR, wherein the CAR comprises an antigen binding domain, an ICOS transmembrane domain, and an ICOS intracellular signaling domain, thereby treating the mammal, wherein the ICOS transmembrane domain comprises the amino acid sequence of SEQ ID NO:
- 12.
A method of treating a human with cancer, the method comprising administering to the human a cell genetically engineered to express a CAR, wherein the CAR comprises an antigen binding domain, an ICOS transmembrane domain, and an ICOS intracellular signaling domain, wherein the cell is selected from the group consisting of a Th17 cell and a Tc17 cell, wherein the ICOS transmembrane domain comprises the amino acid sequence of SEQ ID NO:
- 12.
A method of generating a persisting population of genetically engineered T cells in a human diagnosed with cancer, the method comprising administering to the human a cell genetically engineered to express a CAR, wherein the CAR comprises an antigen binding domain, an ICOS transmembrane domain, and an ICOS intracellular signaling domain, wherein the persisting population of genetically engineered cells persists in the human for at least one month after administration, and wherein the cell is selected from the group consisting of a Th17 cell and a Tc17 cell, and wherein the ICOS transmembrane domain comprises the amino acid sequence of SEQ ID NO:
- 12.
A method of expanding a population of genetically engineered T cells in a human diagnosed with cancer, the method comprising administering to the human a cell genetically engineered to express a CAR, wherein the CAR comprises an antigen binding domain, an ICOS transmembrane domain, and an ICOS intracellular signaling domain, wherein the administered genetically engineered cell is selected from the group consisting of a Th17 cell and a Tc17 cell, further wherein the administered genetically engineered cell produces a population of progeny T cells in the human, and wherein the ICOS transmembrane domain comprises the amino acid sequence of SEQ ID NO:
- 12.
Dependencies are inferred from the claim text.