Use of chimeric antigen receptor-modified T-cells to treat cancer
AssigneeThe Trustees of the University of Pennsylvania
InventorsCarl H. June, Bruce L. Levine, David L. Porter, Michael D. Kalos, Michael C. Milone
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Abstract
The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell to express a CAR wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain.
Claims53
A method for stimulating a T cell-mediated immune response to a target cell population or tissue in a human, the method comprising administering to the human an effective amount of a cell genetically modified to express a CAR wherein the CAR comprises a CD19 antigen binding domain, a transmembrane domain, a costimulatory signaling region comprising 4-1BB, and a CD3 zeta signaling domain comprising the amino acid sequence of SEQ ID NO:
- 24, wherein the CD19 antigen binding domain specifically recognizes CD19 in the target cell population or tissue, wherein the cell is from a human having cancer.
A method of providing an anti-tumor immunity in a human, the method comprising administering to the human an effective amount of a cell genetically modified to express a CAR wherein the CAR comprises a CD19 antigen binding domain, a transmembrane domain, a costimulatory signaling region comprising 4-1BB, and a CD3 zeta signaling domain comprising the amino acid sequence of SEQ ID NO:
- 24, thereby providing an anti-tumor immunity in the human, wherein the cell is from a human having cancer.
A method of treating a human having a disease, disorder or condition associated with an elevated expression of a tumor antigen, the method comprising administering to the human an effective amount of a cell genetically modified to express a CAR wherein the CAR comprises a CD19 antigen binding domain, a transmembrane domain, a costimulatory signaling region comprising 4-1BB, and a CD3 zeta signaling domain comprising the amino acid sequence of SEQ ID NO:
- 24, thereby treating the human, wherein the cell is from a human having cancer.
A method of treating a human with chronic lymphocytic leukemia or acute lymphocytic leukemia, the method comprising administering to the human a T cell genetically engineered to express a CAR wherein the CAR comprises a CD19 antigen binding domain, a transmembrane domain, a costimulatory signaling region comprising 4-1BB, and a CD3 zeta signaling domain comprising the amino acid sequence of SEQ ID NO:
- 24, wherein the T cell is from a human having cancer.
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 T cell genetically engineered to express a CAR wherein the CAR comprises a CD19 antigen binding domain, a transmembrane domain, a costimulatory signaling region comprising 4-1BB, and a CD3 zeta signaling domain comprising the amino acid sequence of SEQ ID NO:
- 24, wherein the persisting population of genetically engineered T cells persists in the human for at least one month after administration, and wherein the T cell is from a human having cancer.
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 T cell genetically engineered to express a CAR wherein the CAR comprises a CD19 antigen binding domain, a transmembrane domain, a costimulatory signaling region comprising 4-1BB, and a CD3 zeta signaling domain comprising the amino acid sequence of SEQ ID NO:
- 24, wherein the administered genetically engineered T cell produces a population of progeny T cells in the human, and wherein the T cell is from a human having cancer.
Dependencies are inferred from the claim text.