In this phase I clinical trial of GPC3-peptide vaccination against pediatric GPC3-expressing solid tumors, treatment was well-tolerated in all eighteen enrolled patients. Disease control was observed in about two thirds of patients over almost 5 years of evaluation. The vaccine induced GPC3-specific cytotoxic T lymphocyte responses in seven patients (almost all of whom were in remission with diagnosed hepatoblastoma), which correlated with high progression-free and overall survival. Antigen-specific T cells were found in the tumor of the one patient evaluated.
The carcinoembryonic antigen glypican-3 (GPC3) is a good target of anticancer immunotherapy against pediatric solid tumors expressing GPC3. In this non-randomized, open-label, phase I clinical trial, we analyzed the safety and efficacy of GPC3-peptide vaccination in patients with pediatric solid tumors. Eighteen patients with pediatric solid tumors expressing GPC3 underwent GPC3-peptide vaccination (intradermal injections every 2 weeks), with the primary endpoint being the safety of GPC3-peptide vaccination and the secondary endpoints being immune response, as measured by interferon (IFN)-gamma enzyme-linked immunospot assay and Dextramer staining, and the clinical outcomes of tumor response, progression free survival (PFS), and overall survival (OS). Our findings indicated that GPC3 vaccination was well tolerated. We observed disease-control rates [complete response (CR)+partial response+stable disease] of 66.7% after 2 months, and although patients in the progression group unable to induce GPC3-peptide-specific cytotoxic T lymphocytes (CTLs) received poor prognoses, patients in the partial-remission and remission groups or those with hepatoblastoma received good prognoses. The GPC3-peptide vaccine induced a GPC3-specific CTL response in seven patients, with PFS and OS significantly longer in patients with high GPC3-specific CTL frequencies than in those with low frequencies. Furthermore, we established GPC3-peptide-specific CTL clones from a resected-recurrent tumor from one patient, with these cells exhibiting GPC3-peptide-specific cytokine secretion. The results of this trial demonstrated that the GPC3-peptide-specific CTLs induced by the GPC3-peptide vaccine infiltrated tumor tissue, and use of the GPC3-peptide vaccine might prevent the recurrence of pediatric solid tumors, especially hepatoblastomas, after a second CR.
Author Info: (1) Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan. (2) Division of Pediatric Oncology, Na
Author Info: (1) Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan. (2) Division of Pediatric Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. (3) Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan. (4) Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan. (5) Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan. (6) Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan. (7) Department of Pediatric Hematology and Oncology, Osaka City General Hospital, Miyakojima-hondori, Miyakojima-ku, Osaka, Japan. (8) Department of Pediatric Hematology and Oncology, Osaka City General Hospital, Miyakojima-hondori, Miyakojima-ku, Osaka, Japan. (9) Department of Pediatrics, St Luke's International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo, Japan. (10) Department of Pediatrics, St Luke's International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo, Japan. (11) Department of Pediatrics, St Luke's International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo, Japan. (12) Division of Pediatric Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan. (13) Department of Pediatric Surgery, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan. (14) Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan. (15) Department of Biomedical Statistics, Innovative Clinical Research Center, Kanazawa University, 13-1, Takara-machi, Kanazawa, Ishikawa, Japan. (16) Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan. (17) Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan. (18) Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan. (19) Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
