Use of the CD2 signaling domain in second-generation chimeric antigen receptors
AssigneeThe Trustees of the University of Pennsylvania
InventorsCarl H. June, John Scholler, Avery D. Posey, Jr.
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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 expressing a CAR having an antigen binding domain, a transmembrane domain, a CD2 signaling domain, and a CD3 zeta signaling domain. The invention also includes incorporating CD2 into the CAR to alter the cytokine production of CAR-T cells in both negative and positive directions.
Claims20
A method of treating a human with cancer, the method comprising:
- administering to the human a T cell genetically engineered to express a chimeric antigen receptor (CAR), wherein the CAR comprises:
- (i) an antigen binding domain, wherein the antigen binding domain targets a tumor antigen selected from the group consisting of CD19, CD20, CD22, ROR1, mesothelin, CD33, IL3Ra, c-Met, PSMA, Glycolipid F77, EGFRvIII, GD-2, NY-ESO-1 TCR, MAGE A3 TCR, and MUC1 (CA15-3), and any combination thereof,
- (ii) a transmembrane domain,
- (iii) a costimulatory signaling region comprising a CD2 signaling domain and a CD28 signaling domain, or a CD2 signaling domain and a 4-1BB signaling domain, wherein the CD2 signaling domain is encoded by a nucleic acid sequence comprising nucleotides 996-1346 of SEQ ID NO:
- 1, and
- (iv) a CD3 zeta signaling domain,
- thereby treating the human.
A method of providing an anti-tumor immunity in a mammal in need thereof, the method comprising:
- administering to the mammal an effective amount of a T cell genetically modified to express a chimeric antigen receptor (CAR),
- wherein the CAR comprises:
- an antigen binding domain that targets a tumor antigen selected from the group consisting of CD19, CD20, CD22, ROR1, mesothelin, CD33, IL3Ra, c-Met, PSMA, Glycolipid F77, EGFRvIII, GD-2, NY-ESO-1 TCR, MAGE A3 TCR, and MUC1 (CA15-3), and any combination thereof,
- a transmembrane domain,
- a costimulatory signaling region comprising a CD2 signaling domain and a CD28 signaling domain, or a CD2 signaling domain and a 4-1BB signaling domain, wherein the CD2 signaling domain is encoded by a nucleic acid sequence comprising nucleotides 996-1346 of SEQ ID NO:
- 1, and
- a CD3 zeta signaling domain.
Dependencies are inferred from the claim text.