Heat shock protein 105 peptide vaccine could induce antitumor immune reactions in a phase I clinical trial

Yasuhiro Shimizu, Toshiaki Yoshikawa, Takashi Kojima, Kayoko Shoda, Kazuto Nosaka, Shoichi Mizuno, Satoshi Wada, Yuki Fujimoto, Tetsuro Sasada, Kenichi Kohashi, Hideaki Bando, Itaru Endo, Tetsuya Nakatsura

研究成果: ジャーナルへの寄稿記事

抄録

Heat shock protein 105 (HSP105) is overexpressed in many cancers, including colorectal cancer (CRC) and esophageal cancer (EC). We carried out a phase I clinical trial of HLA-A24- and HLA-A2-restricted HSP105 peptide vaccines in patients with CRC or EC. In this additional study of the trial, we examined the immunological efficacy of the novel vaccine. Thirty patients with advanced CRC or EC underwent HSP105 peptide vaccination. Immunological responses were evaluated by ex vivo and in vitro γ-interferon enzyme-linked immunospot assays and their correlation with patients’ prognosis was analyzed. The HSP105 peptide vaccines induced peptide-specific CTLs in 15 of 30 patients. Among HLA-A24 patients (n = 15), 7 showed induction of CTLs only ex vivo, whereas among HLA-A2 patients (n = 15), 4 showed the induction ex vivo and 6 in vitro. Heat shock protein 105-specific CTL induction correlated with suppression of cancer progression and was revealed as a potential predictive biomarker for progression-free survival (P =.008; hazard ratio = 3.03; 95% confidence interval, 1.34-6.85) and overall survival (P =.025; hazard ratio = 2.72; 95% confidence interval, 1.13-6.52). Production of cytokines by HSP105 peptide-specific CTLs was observed at the injection sites (skin) and tumor tissues, suggesting that HSP105-specific CTLs not only accumulated at vaccination sites but also infiltrated tumors. Furthermore, we established 2 HSP105 peptide-specific CTL clones, which showed HSP105-specific cytokine secretion and cytotoxicity. Our results suggest that the HSP105 peptide vaccine could induce immunological effects in cancer patients and improve their prognosis.

元の言語英語
ページ(範囲)3049-3060
ページ数12
ジャーナルCancer Science
110
発行部数10
DOI
出版物ステータス出版済み - 10 1 2019

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Clinical Trials, Phase I
Subunit Vaccines
Heat-Shock Proteins
HLA-A24 Antigen
Esophageal Neoplasms
HLA-A2 Antigen
Colorectal Neoplasms
Peptides
Neoplasms
Vaccination
Confidence Intervals
Cytokines
Enzyme-Linked Immunospot Assay
Interferons
Disease-Free Survival
Vaccines
Clone Cells
Biomarkers
Skin

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Shimizu, Y., Yoshikawa, T., Kojima, T., Shoda, K., Nosaka, K., Mizuno, S., ... Nakatsura, T. (2019). Heat shock protein 105 peptide vaccine could induce antitumor immune reactions in a phase I clinical trial. Cancer Science, 110(10), 3049-3060. https://doi.org/10.1111/cas.14165

Heat shock protein 105 peptide vaccine could induce antitumor immune reactions in a phase I clinical trial. / Shimizu, Yasuhiro; Yoshikawa, Toshiaki; Kojima, Takashi; Shoda, Kayoko; Nosaka, Kazuto; Mizuno, Shoichi; Wada, Satoshi; Fujimoto, Yuki; Sasada, Tetsuro; Kohashi, Kenichi; Bando, Hideaki; Endo, Itaru; Nakatsura, Tetsuya.

:: Cancer Science, 巻 110, 番号 10, 01.10.2019, p. 3049-3060.

研究成果: ジャーナルへの寄稿記事

Shimizu, Y, Yoshikawa, T, Kojima, T, Shoda, K, Nosaka, K, Mizuno, S, Wada, S, Fujimoto, Y, Sasada, T, Kohashi, K, Bando, H, Endo, I & Nakatsura, T 2019, 'Heat shock protein 105 peptide vaccine could induce antitumor immune reactions in a phase I clinical trial', Cancer Science, 巻. 110, 番号 10, pp. 3049-3060. https://doi.org/10.1111/cas.14165
Shimizu Y, Yoshikawa T, Kojima T, Shoda K, Nosaka K, Mizuno S その他. Heat shock protein 105 peptide vaccine could induce antitumor immune reactions in a phase I clinical trial. Cancer Science. 2019 10 1;110(10):3049-3060. https://doi.org/10.1111/cas.14165
Shimizu, Yasuhiro ; Yoshikawa, Toshiaki ; Kojima, Takashi ; Shoda, Kayoko ; Nosaka, Kazuto ; Mizuno, Shoichi ; Wada, Satoshi ; Fujimoto, Yuki ; Sasada, Tetsuro ; Kohashi, Kenichi ; Bando, Hideaki ; Endo, Itaru ; Nakatsura, Tetsuya. / Heat shock protein 105 peptide vaccine could induce antitumor immune reactions in a phase I clinical trial. :: Cancer Science. 2019 ; 巻 110, 番号 10. pp. 3049-3060.
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abstract = "Heat shock protein 105 (HSP105) is overexpressed in many cancers, including colorectal cancer (CRC) and esophageal cancer (EC). We carried out a phase I clinical trial of HLA-A24- and HLA-A2-restricted HSP105 peptide vaccines in patients with CRC or EC. In this additional study of the trial, we examined the immunological efficacy of the novel vaccine. Thirty patients with advanced CRC or EC underwent HSP105 peptide vaccination. Immunological responses were evaluated by ex vivo and in vitro γ-interferon enzyme-linked immunospot assays and their correlation with patients’ prognosis was analyzed. The HSP105 peptide vaccines induced peptide-specific CTLs in 15 of 30 patients. Among HLA-A24 patients (n = 15), 7 showed induction of CTLs only ex vivo, whereas among HLA-A2 patients (n = 15), 4 showed the induction ex vivo and 6 in vitro. Heat shock protein 105-specific CTL induction correlated with suppression of cancer progression and was revealed as a potential predictive biomarker for progression-free survival (P =.008; hazard ratio = 3.03; 95{\%} confidence interval, 1.34-6.85) and overall survival (P =.025; hazard ratio = 2.72; 95{\%} confidence interval, 1.13-6.52). Production of cytokines by HSP105 peptide-specific CTLs was observed at the injection sites (skin) and tumor tissues, suggesting that HSP105-specific CTLs not only accumulated at vaccination sites but also infiltrated tumors. Furthermore, we established 2 HSP105 peptide-specific CTL clones, which showed HSP105-specific cytokine secretion and cytotoxicity. Our results suggest that the HSP105 peptide vaccine could induce immunological effects in cancer patients and improve their prognosis.",
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AU - Mizuno, Shoichi

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AU - Fujimoto, Yuki

AU - Sasada, Tetsuro

AU - Kohashi, Kenichi

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AU - Endo, Itaru

AU - Nakatsura, Tetsuya

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