Six-transmembrane epithelial antigen of the prostate and enhancer of zeste homolog 2 as immunotherapeutic targets for lung cancer

Satoshi Hayashi, Takumi Kumai, Yoshiya Matsuda, Naoko Aoki, Keisuke Sato, Shoji Kimura, Masahiro Kitada, Masatoshi Tateno, Esteban Celis, Hiroya Kobayashi

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: T-cell based immunotherapy for lung cancer (LC) could be a promising and novel therapeutic approach. Six-transmembrane epithelial antigen of the prostate (STEAP) and the polycomb group protein enhancer of zeste homolog 2 (EZH2) are highly expressed in LC and since the expression of molecules in normal tissue is significantly lower as compared to tumor cells, these proteins are considered as potential tumor-associated antigens (TAAs) for developing T-cell based immunotherapy.Methods: We assessed the capacity of predicted CD4 T-cell epitopes from STEAP and EZH2 to induce anti-tumor immune responses to LC cell lines.Results: Out of several predicted epitopes, two synthetic peptides, STEAP 281-296 and EZH2 95-109 , were effective in inducing CD4 T-cell responses that were restricted by HLA-DR1, DR15, or DR53 molecules, indicating that the peptides function as promiscuous T-cell epitopes. Moreover, STEAP 281-296 and EZH2 95-109 -reactive T-cells could directly recognize STEAP or EZH2 expressing LC cells in an HLA-DR restricted manner. In addition, some STEAP-reactive T-cells responded to STEAP+ tumor cell lysates presented by autologous dendric cells. Most significantly, both of these peptides were capable of stimulating in vitro T-cell responses in patients with LC.Conclusions: Peptides STEAP 281-296 and EZH2 95-109 function as strong CD4 T-cell epitopes that can elicit effective anti-tumor T-cell responses against STEAP or EZH2 expressing LC. These observations may facilitate the translation of T-cell based immunotherapy into the clinic for the treatment of LC.

Original languageEnglish (US)
Article number191
JournalJournal of Translational Medicine
Volume9
Issue number1
DOIs
StatePublished - Nov 5 2011

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T-cells
Prostate
Lung Neoplasms
Antigens
T-Lymphocytes
Tumors
T-Lymphocyte Epitopes
Immunotherapy
Peptides
Neoplasm Antigens
Cells
HLA-DR1 Antigen
Polycomb-Group Proteins
Enhancer of Zeste Homolog 2 Protein
Neoplasms
Molecules
HLA-DR Antigens
Epitopes
Cell Line
Tissue

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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Six-transmembrane epithelial antigen of the prostate and enhancer of zeste homolog 2 as immunotherapeutic targets for lung cancer. / Hayashi, Satoshi; Kumai, Takumi; Matsuda, Yoshiya; Aoki, Naoko; Sato, Keisuke; Kimura, Shoji; Kitada, Masahiro; Tateno, Masatoshi; Celis, Esteban; Kobayashi, Hiroya.

In: Journal of Translational Medicine, Vol. 9, No. 1, 191, 05.11.2011.

Research output: Contribution to journalArticle

Hayashi, Satoshi ; Kumai, Takumi ; Matsuda, Yoshiya ; Aoki, Naoko ; Sato, Keisuke ; Kimura, Shoji ; Kitada, Masahiro ; Tateno, Masatoshi ; Celis, Esteban ; Kobayashi, Hiroya. / Six-transmembrane epithelial antigen of the prostate and enhancer of zeste homolog 2 as immunotherapeutic targets for lung cancer. In: Journal of Translational Medicine. 2011 ; Vol. 9, No. 1.
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AU - Sato, Keisuke

AU - Kimura, Shoji

AU - Kitada, Masahiro

AU - Tateno, Masatoshi

AU - Celis, Esteban

AU - Kobayashi, Hiroya

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N2 - Background: T-cell based immunotherapy for lung cancer (LC) could be a promising and novel therapeutic approach. Six-transmembrane epithelial antigen of the prostate (STEAP) and the polycomb group protein enhancer of zeste homolog 2 (EZH2) are highly expressed in LC and since the expression of molecules in normal tissue is significantly lower as compared to tumor cells, these proteins are considered as potential tumor-associated antigens (TAAs) for developing T-cell based immunotherapy.Methods: We assessed the capacity of predicted CD4 T-cell epitopes from STEAP and EZH2 to induce anti-tumor immune responses to LC cell lines.Results: Out of several predicted epitopes, two synthetic peptides, STEAP 281-296 and EZH2 95-109 , were effective in inducing CD4 T-cell responses that were restricted by HLA-DR1, DR15, or DR53 molecules, indicating that the peptides function as promiscuous T-cell epitopes. Moreover, STEAP 281-296 and EZH2 95-109 -reactive T-cells could directly recognize STEAP or EZH2 expressing LC cells in an HLA-DR restricted manner. In addition, some STEAP-reactive T-cells responded to STEAP+ tumor cell lysates presented by autologous dendric cells. Most significantly, both of these peptides were capable of stimulating in vitro T-cell responses in patients with LC.Conclusions: Peptides STEAP 281-296 and EZH2 95-109 function as strong CD4 T-cell epitopes that can elicit effective anti-tumor T-cell responses against STEAP or EZH2 expressing LC. These observations may facilitate the translation of T-cell based immunotherapy into the clinic for the treatment of LC.

AB - Background: T-cell based immunotherapy for lung cancer (LC) could be a promising and novel therapeutic approach. Six-transmembrane epithelial antigen of the prostate (STEAP) and the polycomb group protein enhancer of zeste homolog 2 (EZH2) are highly expressed in LC and since the expression of molecules in normal tissue is significantly lower as compared to tumor cells, these proteins are considered as potential tumor-associated antigens (TAAs) for developing T-cell based immunotherapy.Methods: We assessed the capacity of predicted CD4 T-cell epitopes from STEAP and EZH2 to induce anti-tumor immune responses to LC cell lines.Results: Out of several predicted epitopes, two synthetic peptides, STEAP 281-296 and EZH2 95-109 , were effective in inducing CD4 T-cell responses that were restricted by HLA-DR1, DR15, or DR53 molecules, indicating that the peptides function as promiscuous T-cell epitopes. Moreover, STEAP 281-296 and EZH2 95-109 -reactive T-cells could directly recognize STEAP or EZH2 expressing LC cells in an HLA-DR restricted manner. In addition, some STEAP-reactive T-cells responded to STEAP+ tumor cell lysates presented by autologous dendric cells. Most significantly, both of these peptides were capable of stimulating in vitro T-cell responses in patients with LC.Conclusions: Peptides STEAP 281-296 and EZH2 95-109 function as strong CD4 T-cell epitopes that can elicit effective anti-tumor T-cell responses against STEAP or EZH2 expressing LC. These observations may facilitate the translation of T-cell based immunotherapy into the clinic for the treatment of LC.

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