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Recognition of Prostate and Breast Tumor Cells by Helper T Lymphocytes Specific for a Prostate and Breast Tumor-Associated Antigen, TARP

Authors' Affiliations: ¹ Department of Pathology, Asahikawa Medical College, Asahikawa, Japan; and ² Department of Pediatrics and Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana

Requests for reprints: Esteban Celis, Tumor Immunology/Immunotherapy Program, Lousiana State University Health Sciences Center, Room 526, 533 Bolivar Street, New Orleans, LA 70112. Phone: 504-568-3280; Fax: 504-568-3277; E-mail: ecelis{at}lsuhsc.edu.

Purpose: T cell–based immunotherapy via the in vitro or in vivo expansion of prostate tumor-associated antigen (TAA)–specific T lymphocytes is one of the most promising therapeutic approaches to treat prostate cancer. T-cell alternate reading frame protein (TARP) is a mitochondrial protein that is specifically expressed in prostate epithelial cells. We have done experiments aimed at identifying helper T lymphocyte (HTL) epitopes for TARP for the design of T cell–based immunotherapy for prostate cancer.

Experimental Design: Dendritic cells from normal donors were pulsed with synthetic peptides derived from TARP, which were predicted to serve as HTL epitopes. These dendritic cells were used to stimulate CD4⁺ T cells in vitro to trigger HTL responses against TARP. T-cell responses to these peptides were also studied with lymphocytes from prostate cancer patients.

Results: The two peptides, TARP_1-14 and TARP_14-27, were shown to elicit effective in vitro HTL responses using lymphocytes from both normal volunteers and prostate cancer patients. Peptide TARP_1-14-reactive HTLs were found restricted by HLA-DR53 and could recognize naturally processed protein antigen derived from tumor cells, which was presented by autologous dendritic cells. Most significantly, stimulation with peptide TARP_14-27 generated four HTL lines restricted by HLA-DR1, HLA-DR9, HLA-DR13, and HLA-DR15, some of which capable of recognizing naturally processed antigens presented by dendritic cell or directly by TARP-positive tumor cells.

Conclusions: Our results show that TARP constitutes a TAA that can be recognized by tumor-reactive HTL. The newly described TARP epitopes could be used to optimize and improve T-cell epitope–based immunotherapy against prostate and other tumors expressing TARP.

Key Words: Helper T cells • TARP • immunotherapy • tumor vaccines • peptide epitopes

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