Recognition of prostate and breast tumor cells by helper T lymphocytes specific for a prostate and breast tumor-associated antigen, TARP.

Abstract

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.

• Authors: Hiroya Kobayashi, Toshihiro Nagato, Kensuke Oikawa, Keisuke Sato, Shoji Kimura, Naoko Aoki, Ryusuke Omiya, Masatoshi Tateno, Esteban Celis
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 11 Issue 10 Pg. 3869-78 (May 15 2005) ISSN: 1078-0432 [Print] United States
• PMID: 15897588 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, Neoplasm
• Cancer Vaccines
• Epitopes
• Nuclear Proteins
• TARP

Topics

• Antigen Presentation
• Antigens, Neoplasm
• Breast Neoplasms (immunology, pathology)
• CD4-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (immunology)
• Dendritic Cells
• Epitopes
• Female
• Humans
• Immunotherapy
• Male
• Nuclear Proteins (immunology)
• Prostatic Neoplasms (immunology, pathology)
• T-Lymphocytes, Helper-Inducer (immunology)
• Tumor Cells, Cultured