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

• Published in: Journal of translational medicine 2011-11, Vol.9 (1), p.191-191, Article 191
• Main Authors: Hayashi, Satoshi, Kumai, Takumi, Matsuda, Yoshiya, Aoki, Naoko, Sato, Keisuke, Kimura, Shoji, Kitada, Masahiro, Tateno, Masatoshi, Celis, Esteban, Kobayashi, Hiroya
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - blood; Adenocarcinoma - immunology; Adenocarcinoma - pathology; Adenocarcinoma - therapy; Adult; Aged; Aged, 80 and over; Alleles; Animals; Antigen Presentation - immunology; Antigens, Neoplasm - immunology; Antigens, Neoplasm - metabolism; Care and treatment; CD4-Positive T-Lymphocytes - immunology; Cell Line; Chemotherapy; Clone Cells; Cloning; Cytotoxicity, Immunologic; DNA-Binding Proteins - immunology; DNA-Binding Proteins - metabolism; Enhancer of Zeste Homolog 2 Protein; Epitopes - immunology; Female; Gene mutations; Genetic aspects; Granzymes - metabolism; Health aspects; HLA-DR Antigens - immunology; Humans; Immunotherapy; Lung cancer; Lung cancer, Non-small cell; Lung Neoplasms - blood; Lung Neoplasms - immunology; Lung Neoplasms - pathology; Lung Neoplasms - therapy; Lymphocytes; Male; Mass spectrometry; Mice; Middle Aged; Molecular Targeted Therapy; Oxidoreductases - immunology; Oxidoreductases - metabolism; Peptides - immunology; Polycomb Repressive Complex 2; Risk factors; Studies; Tetanus; Transcription Factors - immunology; Transcription Factors - metabolism; Tumors
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/1479-5876-9-191

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. We assessed the capacity of predicted CD4 T-cell epitopes from STEAP and EZH2 to induce anti-tumor immune responses to LC cell lines. Out of several predicted epitopes, two synthetic peptides, STEAP281-296 and EZH295-109, 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, STEAP281-296 and EZH295-109-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. Peptides STEAP281-296 and EZH295-109 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.