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)-γ
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.