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 receptor γ-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 transduced with a lentiviral vector encoding the TARP-TCR proliferated well when exposed to peptide-specific stimuli. These cells exerted peptide-specific IFN-γ 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 relevant HLA-A2 epitope of TARP. To our knowledge this report on engineering of T cells with a TCR directed against an antigen specifically expressed by prostate cells is unique.
Written by:
Hillerdal V, Nilsson B, Carlsson B, Eriksson F, Essand M. Are you the author?
Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Reference: Proc Natl Acad Sci U S A. 2012 Sep 25;109(39):15877-81.
doi: 10.1073/pnas.1209042109
PubMed Abstract
PMID: 23019373
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