T cell receptor-deficient chimeric antigen receptor T-cells and methods of use thereof
AssigneeNational University of Singapore
InventorsDario Campana, Takahiro Kamiya
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Abstract
The present invention provides compositions comprising a protein expression blocker or PEBL comprising a target-binding molecule and localizing domain, and methods of using such compositions in cancer therapy. PEBLs are useful as a blockade of expression of target surface receptors (peptides or antigens) in immune cells. Also provided herein are CD3/TCRαβ-deficient T cells and CD3/TCRαβ-deficient chimeric antigen receptor T cells that express such PEBLs.
Claims19
A method of treating a CD19-positive or a CD3-positive cancer in a patient in need thereof, comprising administering a therapeutically effective amount of engineered CD3/TCRαβ-deficient T cells to the patient,
- wherein the engineered CD3/TCRαβ-deficient T cells comprise:
- (i) a chimeric antigen receptor (CAR) that binds CD3 or CD 19;
- and
- (ii) a polypeptide comprising a target-binding molecule connected by a linker to a localizing domain,
- wherein the target-binding molecule comprises an antibody that binds a CD3/TCRαβ complex protein,
- wherein
- (a) the linker comprises a transmembrane domain having the amino acid sequence set forth in SEQ ID NO:
- 7, and the localizing domain comprises KKXX, where X is any amino acid (SEQ ID NO:35), or
- (b) the linker and localizing domain together comprise any one of SEQ ID NOs:16-26.
A method of reducing or eliminating the likelihood of graft-versus-host disease in an individual receiving therapeutic T cell treatment, comprising administering engineered CD3/TCRαβ-deficient T cells to the individual, wherein the engineered CD3/TCRαβ-deficient T cells comprise a polypeptide comprising a target-binding molecule connected by a linker to a localizing domain,
- wherein the target-binding molecule comprises an antibody that binds a CD3/TCRαβ complex protein,
- wherein
- a) the linker comprises a transmembrane domain having the amino acid sequence set forth in SEQ ID NO:
- 7, and the localizing domain comprises KKXX, where X is any amino acid (SEQ ID NO:35), or
- b) the linker and localizing domain together comprise any one of SEQ ID NOs:
- 16-26.
Dependencies are inferred from the claim text.