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 by ex vivo IFNγ 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.

Cancer immunotherapy‐targeted glypican‐3 or neoantigens

“…We also observed antitumor effects in a Nagoya University (Nagoya, Japan) clinical trial (UMIN Clinical Trials Registry: 000003696) of GPC3 peptide vaccines against OCCC (Figure 2f), 19 highlighting the versatility of this vaccine (Table 1). 20 The primary end-point was disease control rate at 6 months. In the results, two cases showed partial response one case showed stable disease.…”

Higher human lymphocyte antigen class I expression in early‐stage cancer cells leads to high sensitivity for cytotoxic T lymphocytes

“…Previously, we identified glypican-3 (GPC3), which is a tumor-associated antigen, and conducted clinical trials of GPC3-peptide vaccination against patients with several cancer types, including advanced HCC. 26,[39][40][41][42][43] As a result of these trials, we found an adequate anti-tumor effect in advanced HCC with this peptide vaccination, which led to a better OS in HCC patients. 26,39 We also developed a method of immunotherapy using intratumoral peptide injection that could induce additional peptide loading onto tumor cells.…”

“…In this study, we demonstrated that antigen‐specific CTL had high reactivity toward HCC cells with strongly positive HLA class I expression (Figure ). Previously, we identified glypican‐3 (GPC3), which is a tumor‐associated antigen, and conducted clinical trials of GPC3‐peptide vaccination against patients with several cancer types, including advanced HCC . As a result of these trials, we found an adequate anti–tumor effect in advanced HCC with this peptide vaccination, which led to a better OS in HCC patients .…”

Tumor Microenvironment: Extracellular Matrix Alterations Influence Tumor Progression

“…Glypican-3 represents a promising immunotherapeutic target. Different GPC3-targeting therapies have been developed: the use of humanized anti-GPC3 cytotoxic antibodies, the treatment with peptide/DNA vaccines, immunotoxin therapies, and genetic therapies (107,(157)(158)(159)(160)(161)(162).…”