Compositions and methods of T cell receptor VB family member targeting for the treatment of T cell associated disease
AssigneeThe Trustees of the University of Pennsylvania
InventorsDaniel J. Powell, Stephen J. Schuster, Lauren Shaw
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Abstract
Provided is a chimeric antigen receptor (CAR) comprising a domain that binds a Vβ region of a T cell receptor. Also provided is a T cell genetically modified to express the CAR, and methods for treating cancer in a subject in need thereof.
Claims19
A CAR comprising an extracellular domain that binds a Vβ region of a T cell receptor, a transmembrane domain, and an intracellular signaling domain, wherein the intracellular signaling domain comprises a costimulatory signaling region;
- wherein the extracellular domain that binds a Vβ region is selected from the group consisting of an antibody, a Fab, and an scFv;
- and
- wherein the extracellular domain comprises a light chain variable region (VL) comprising three light chain complementarity determining regions 1-3 (LCDR1-3) and a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions 1-3 (HCDR1-3), and wherein the Vβ region is:
- (a) Vβ12, wherein the LCDRs 1-3 comprise the sequences of SEQ ID NOs:
- 62-64, respectively, and the HCDRs 1-3 comprise the sequences of SEQ ID NOs:
- 58-60, respectively;
- (b) Vβ5.1, wherein the LCDRs 1-3 comprise the sequences of SEQ ID NOs:
- 102-104, respectively, and the HCDRs 1-3 comprise the sequences of SEQ ID NOs:
- 98-100, respectively;
- or
- (c) Vβ4, wherein the LCDRs 1-3 comprise the sequences of SEQ ID NOs:
- 94-96, respectively, and the HCDRs 1-3 comprise the sequences of SEQ ID NOs:
- 90-92, respectively.
A nucleic acid encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an extracellular domain that binds a Vβ region of a T cell receptor, a transmembrane domain, and an intracellular signaling domain, wherein the intracellular signaling domain comprises a costimulatory signaling region;
- wherein the extracellular domain that binds a Vβ region is selected from the group consisting of an antibody, a Fab, and a scFv;
- and
- wherein the extracellular domain comprises a light chain variable region (VL) comprising three light chain complementarity determining regions 1-3 (LCDR1-3) and a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions 1-3 (HCDR1-3), and wherein the Vβ region is:
- (a) Vβ12, wherein the LCDRs 1-3 comprise the sequences of SEQ ID NOs:
- 62-64, respectively, and the HCDRs 1-3 comprise the sequences of SEQ ID NOs:
- 58-60, respectively;
- (b) Vβ5.1, wherein the LCDRs 1-3 comprise the sequences of SEQ ID NOs:
- 102-104, respectively, and the HCDRs 1-3 comprise the sequences of SEQ ID NOs:
- 98-100, respectively;
- or
- (c) Vβ4, wherein the LCDRs 1-3 comprise the sequences of SEQ ID NOs:
- 94-96, respectively, and the HCDRs 1-3 comprise the sequences of SEQ ID NOs:
- 90-92, respectively.
Dependencies are inferred from the claim text.