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Heat shock protein 105 peptide vaccine could induce antitumor immune reactions in a phase I clinical trial.
- Source :
-
Cancer science [Cancer Sci] 2019 Oct; Vol. 110 (10), pp. 3049-3060. Date of Electronic Publication: 2019 Sep 19. - Publication Year :
- 2019
-
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.<br /> (© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
- Subjects :
- Adult
Aged
Cancer Vaccines immunology
Cell Line, Tumor
Colorectal Neoplasms immunology
Cytokines metabolism
Disease-Free Survival
Esophageal Neoplasms immunology
Female
HLA-A2 Antigen metabolism
HLA-A24 Antigen metabolism
Hep G2 Cells
Humans
Male
Middle Aged
Prognosis
T-Lymphocytes, Cytotoxic immunology
Treatment Outcome
Vaccines, Subunit administration & dosage
Vaccines, Subunit immunology
Cancer Vaccines administration & dosage
Colorectal Neoplasms drug therapy
Esophageal Neoplasms drug therapy
HSP110 Heat-Shock Proteins chemistry
HSP110 Heat-Shock Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1349-7006
- Volume :
- 110
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cancer science
- Publication Type :
- Academic Journal
- Accession number :
- 31390678
- Full Text :
- https://doi.org/10.1111/cas.14165