title: 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 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 TARP(4-13) 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.
authors.affiliation: Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Victoria
authors.initials: V
authors.lastname: Hillerdal
authors.forename: Berith
authors.initials: B
authors.lastname: Nilsson
authors.forename: Björn
authors.initials: B
authors.lastname: Carlsson
authors.forename: Fredrik
authors.initials: F
authors.lastname: Eriksson
authors.forename: Magnus
authors.initials: M
authors.lastname: Essand
mesh_terms: D019264:Adoptive Transfer; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D060846:Cell Engineering; D045744:Cell Line, Tumor; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D009687:Nuclear Proteins; D011948:Receptors, Antigen, T-Cell; C413185:TARP