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

Cancer Sci. 2019 Oct;110(10):3049-3060. doi: 10.1111/cas.14165. Epub 2019 Sep 19.


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.

Keywords: cancer vaccine; cytokine; cytotoxic T lymphocyte; heat shock protein 105; human leukocyte antigen.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / immunology
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / immunology
  • Cytokines / metabolism
  • Disease-Free Survival
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / immunology
  • Female
  • HLA-A2 Antigen / metabolism
  • HLA-A24 Antigen / metabolism
  • HSP110 Heat-Shock Proteins / chemistry*
  • HSP110 Heat-Shock Proteins / metabolism*
  • Hep G2 Cells
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • T-Lymphocytes, Cytotoxic / immunology
  • Treatment Outcome
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / immunology


  • Cancer Vaccines
  • Cytokines
  • HLA-A2 Antigen
  • HLA-A24 Antigen
  • HSP110 Heat-Shock Proteins
  • Vaccines, Subunit