TY - JOUR
T1 - Phase I study of glypican-3-derived peptide vaccine therapy for patients with refractory pediatric solid tumors
AU - Tsuchiya, Nobuhiro
AU - Hosono, Ako
AU - Yoshikawa, Toshiaki
AU - Shoda, Kayoko
AU - Nosaka, Kazuto
AU - Shimomura, Manami
AU - Hara, Junichi
AU - Nitani, Chika
AU - Manabe, Atsushi
AU - Yoshihara, Hiroki
AU - Hosoya, Yosuke
AU - Kaneda, Hide
AU - Kinoshita, Yoshiaki
AU - Kohashi, Kenichi
AU - Yoshimura, Kenichi
AU - Fujinami, Norihiro
AU - Saito, Keigo
AU - Mizuno, Shoichi
AU - Nakatsura, Tetsuya
N1 - Funding Information:
This work was supported in part by the National Cancer Center Research and Development Fund (25-A-7) and (28-A-8), as well as Health and Labor Science Research Grants for Clinical Research on Applying Health Technology and Research for Promotion of Cancer Control Programmes, Japan and joint research funding from Takeda Pharmaceutical Co, Ltd. This work was supported in part by the National Cancer Center Research and Development Fund (25-A-7 and 28-A-8), as well as Health and Labor Science Research Grants for Clinical Research on Applying Health Technology and Research for Promotion of Cancer Control Programmes, Japan.
Publisher Copyright:
© 2018 The Author(s). Published with license by Taylor & Francis Group, LLC. © 2018, Nobuhiro Tsuchiya, Ako Hosono, Toshiaki Yoshikawa, Kayoko Shoda, Kazuto Nosaka, Manami Shimomura, Junichi Hara, Chika Nitani, Atsushi Manabe, Hiroki Yoshihara, Yosuke Hosoya, Hide Kaneda, Yoshiaki Kinoshita, Kenichi Kohashi, Kenichi Yoshimura, Norihiro Fujinami, Keigo Saito, Shoichi Mizuno, and Tetsuya Nakatsura.
PY - 2018/1/2
Y1 - 2018/1/2
N2 - 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.
AB - 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.
KW - CTL
KW - glypican-3 (GPC3)
KW - pediatric solid tumors
KW - peptide vaccine
KW - phase I
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U2 - 10.1080/2162402X.2017.1377872
DO - 10.1080/2162402X.2017.1377872
M3 - Article
C2 - 29296538
AN - SCOPUS:85030150293
SN - 2162-4011
VL - 7
JO - OncoImmunology
JF - OncoImmunology
IS - 1
M1 - e1377872
ER -
