T cells engineered with a T cell receptor against the prostate antigen TARP specifically kill HLA-A2+ prostate and breast cancer cells

Abstract

To produce genetically engineered T cells directed against prostate and breast cancer cells,we have cloned the T-cell receptor recognizing the HLA-A2-restricted T-cell recptor ã-chain alternate reading-frame protein (TARP)4-13 epitope. TARP is a protein exclusively expressed in normal prostate epithelium and in adenocarcinomas of the prostate and breast. Peripheral blood T cells transducedwith a lentiviral vector encoding the TARP-TCR proliferated well when exposed to peptidespecific stimuli. These cells exerted peptide-specific IFN-ã production and cytotoxic activity. Importantly, HLA-A2+ prostate and breast cancer cells expressing TARP were also killed, demonstrating that the TARP4-13 epitope is a physiologically relevant target for T-cell therapy of prostate and breast cancer. In conclusion,we present the cloning of a T cell receptor (TCR) directed against a physiologically relevantHLAA2 epitope of TARP. To our knowledge this report onengineeringof T cells with a TCR directed against an antigen specifically expressed by prostate cells is unique.