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

Hiroya Kobayashi, Toshihiro Nagato, Kensuke Oikawa, Keisuke Sato, Shoji Kimura, Naoko Aoki, Ryusuke Omiya, Masatoshi Tateno, Esteban Celis

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 TARP14-27, were shown to elicit effective in vitro HTL responses using lymphocytes from both normal volunteers and prostate cancer patients. Peptide TARP1-14-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 TARP14-27 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.

Original languageEnglish (US)
Pages (from-to)3869-3878
Number of pages10
JournalClinical Cancer Research
Volume11
Issue number10
DOIs
StatePublished - May 15 2005

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Reading Frames
Neoplasm Antigens
Helper-Inducer T-Lymphocytes
Prostate
Breast Neoplasms
T-Lymphocytes
Proteins
Dendritic Cells
T-Lymphocyte Epitopes
Prostatic Neoplasms
Immunotherapy
Peptide T
Peptides
HLA-DR1 Antigen
Lymphocytes
Neoplasms
Mitochondrial Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Recognition of prostate and breast tumor cells by helper T lymphocytes specific for a prostate and breast tumor-associated antigen, TARP. / Kobayashi, Hiroya; Nagato, Toshihiro; Oikawa, Kensuke; Sato, Keisuke; Kimura, Shoji; Aoki, Naoko; Omiya, Ryusuke; Tateno, Masatoshi; Celis, Esteban.

In: Clinical Cancer Research, Vol. 11, No. 10, 15.05.2005, p. 3869-3878.

Research output: Contribution to journalArticle

Kobayashi, Hiroya ; Nagato, Toshihiro ; Oikawa, Kensuke ; Sato, Keisuke ; Kimura, Shoji ; Aoki, Naoko ; Omiya, Ryusuke ; Tateno, Masatoshi ; Celis, Esteban. / Recognition of prostate and breast tumor cells by helper T lymphocytes specific for a prostate and breast tumor-associated antigen, TARP. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 10. pp. 3869-3878.
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T1 - Recognition of prostate and breast tumor cells by helper T lymphocytes specific for a prostate and breast tumor-associated antigen, TARP

AU - Kobayashi, Hiroya

AU - Nagato, Toshihiro

AU - Oikawa, Kensuke

AU - Sato, Keisuke

AU - Kimura, Shoji

AU - Aoki, Naoko

AU - Omiya, Ryusuke

AU - Tateno, Masatoshi

AU - Celis, Esteban

PY - 2005/5/15

Y1 - 2005/5/15

N2 - 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 TARP14-27, were shown to elicit effective in vitro HTL responses using lymphocytes from both normal volunteers and prostate cancer patients. Peptide TARP1-14-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 TARP14-27 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.

AB - 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 TARP14-27, were shown to elicit effective in vitro HTL responses using lymphocytes from both normal volunteers and prostate cancer patients. Peptide TARP1-14-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 TARP14-27 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.

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