title: Efficacy of glypican-3-derived peptide vaccine therapy on the survival of patients with refractory ovarian clear cell carcinoma.
abstract: Compared with other epithelial ovarian carcinoma subtypes, ovarian clear cell carcinoma (OCCC) has been recognized to show chemoresistance. Therefore, new treatment modalities are required for patients with OCCC that is refractory to chemotherapy. The carcinoembryonic antigen glypican-3 (GPC3) is expressed by approximately half of OCCC and is a promising immunotherapeutic target. The purpose of this study was to evaluate the effect of GPC3 peptide vaccine against refractory OCCC patients. We conducted a phase II trial with a GPC3-derived peptide vaccine in OCCC patients. Immunological responses were analyzed byex vivoIFNγ ELISPOT assay. We also evaluated control subjects, who received best supportive care without vaccinations during the same period. Thirty-two patients with refractory OCCC were enrolled between July 2010 and September 2015, and underwent GPC3 peptide vaccination. Fifteen patients were vaccinated less than six times because their general condition progressively deteriorated, and 17 patients were vaccinated at least six times. Three patients showed a partial response as the best overall response. The GPC3 peptide vaccine induced a GPC3-specific CTL response in 15 out of 24 patients who had PBMCs collected three times or more. The prognosis of palliative care patients without GPC3 peptide vaccinations was significantly poorer than that of those with GPC3 peptide vaccinations (post cancer-treatment survival:p= 0.002). Although the disease control rate was not high, our results suggest that GPC3 peptide vaccinations may hold a significant impact to prolong survival of patients with refractory OCCC, allowing them to maintain quality of life with no serious toxicities.
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine , Showa-ku, Nagoya, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine , Showa-ku, Nagoya, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Sakata
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine , Showa-ku, Nagoya, Japan.
authors.forename: Fumi
authors.initials: F
authors.lastname: Utsumi
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine , Showa-ku, Nagoya, Japan.
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Sekiya
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine , Showa-ku, Nagoya, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kajiyama
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine , Showa-ku, Nagoya, Japan.
authors.forename: Kiyosumi
authors.initials: K
authors.lastname: Shibata
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine , Showa-ku, Nagoya, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Kikkawa
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center , Kashiwa, Chiba, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakatsura
keywords: Clear cell carcinoma; cytotoxic T lymphocyte; glypican-3; peptide vaccine; refractory ovarian cancer