PMID- 30430205 OWN - NLM STAT- MEDLINE DCOM- 20190225 LR - 20200225 IS - 1432-0851 (Electronic) IS - 0340-7004 (Print) IS - 0340-7004 (Linking) VI - 68 IP - 2 DP - 2019 Feb TI - A phase I clinical study of a cocktail vaccine of Wilms' tumor 1 (WT1) HLA class I and II peptides for recurrent malignant glioma. PG - 331-340 LID - 10.1007/s00262-018-2274-1 [doi] AB - PURPOSE: The safety and clinical efficacy of WT1 human leukocyte antigen (HLA) class I peptide vaccine have been established, but the safety of a cocktail vaccine of WT1 HLA class I and II peptides has not. To verify its safety, we performed a phase I clinical trial for patients with recurrent malignant gliomas and assessed the immunological responses and survival data. PATIENTS AND METHODS: Fourteen HLA-A*24:02-positive patients with recurrent malignant glioma (2 with grade 3, 12 with grade 4) were enrolled. Every week, the patients received alternately a vaccine containing 3 mg of WT1 HLA-A*24:02-restricted (HLA class I) peptide and a cocktail vaccine of the HLA class I peptide and one of 0.75, 1.5 or 3 mg of the WT1 HLA class II peptide. For patients who showed no significant adverse effects within 6 weeks, the WT1 vaccine was continued at 2-4-week intervals. RESULTS: Eleven of the 14 patients completed WT1 vaccination for 6 weeks, while 3 patients dropped out earlier due to disease progression. All patients showed grade I level of skin disorders at the injection sites. No grade III/IV toxicity or dose-limiting toxicity was observed for any dose of WT1 HLA class II peptide. Six of the 14 patients had stable disease at 6 weeks. Median OS and 1-year OS rates were 24.7 weeks and 36%, respectively. CONCLUSION: The safety of a cocktail vaccine of WT1 HLA class I and II peptides for malignant gliomas was verified. This vaccine is, therefore, considered promising for patients with recurrent malignant glioma. FAU - Tsuboi, Akihiro AU - Tsuboi A AUID- ORCID: 0000-0003-3182-2456 AD - Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka, 565-0871, Japan. tsuboi@cit.med.osaka-u.ac.jp. FAU - Hashimoto, Naoya AU - Hashimoto N AD - Department of Neurosurgery, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan. AD - Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan. FAU - Fujiki, Fumihiro AU - Fujiki F AD - Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka, Japan. FAU - Morimoto, Soyoko AU - Morimoto S AD - Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka, 565-0871, Japan. FAU - Kagawa, Naoki AU - Kagawa N AD - Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan. FAU - Nakajima, Hiroko AU - Nakajima H AD - Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka, Japan. FAU - Hosen, Naoki AU - Hosen N AD - Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan. FAU - Nishida, Sumiyuki AU - Nishida S AD - Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka, Japan. FAU - Nakata, Jun AU - Nakata J AD - Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka, 565-0871, Japan. FAU - Morita, Satoshi AU - Morita S AD - Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan. FAU - Sakamoto, Junichi AU - Sakamoto J AD - Tokai Central Hospital, Kakamigahara, Japan. FAU - Oji, Yusuke AU - Oji Y AD - Department of Functional Diagnostic Sciences, Osaka University Graduate School of Medicine, Osaka, Japan. FAU - Oka, Yoshihiro AU - Oka Y AD - Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan. AD - Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka, Japan. AD - Department of Immunopathology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan. FAU - Sugiyama, Haruo AU - Sugiyama H AD - Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka, Japan. LA - eng GR - 26462179/Grants-in-Aid for Scientific Research of Japan Society/ PT - Clinical Trial, Phase I PT - Journal Article DEP - 20181114 PL - Germany TA - Cancer Immunol Immunother JT - Cancer immunology, immunotherapy : CII JID - 8605732 RN - 0 (Cancer Vaccines) RN - 0 (HLA-A*24:02 antigen) RN - 0 (HLA-A24 Antigen) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Vaccines, Subunit) RN - 0 (WT1 Proteins) SB - IM MH - Adult MH - Brain Neoplasms/*drug therapy/immunology/pathology MH - Cancer Vaccines/immunology/*therapeutic use MH - Female MH - Glioma/*drug therapy/immunology/pathology MH - HLA-A24 Antigen/immunology MH - Histocompatibility Antigens Class II/immunology MH - Humans MH - Male MH - Middle Aged MH - Neoplasm Recurrence, Local MH - Survival Analysis MH - Treatment Outcome MH - Vaccination/methods MH - Vaccines, Subunit/immunology/*therapeutic use MH - WT1 Proteins/immunology PMC - PMC6394509 OTO - NOTNLM OT - Cancer immunotherapy OT - Cancer vaccine OT - HLA class II peptide OT - Malignant glioma OT - Peptide vaccine OT - WT1 COIS- The authors declare that they have no conflict of interest. EDAT- 2018/11/16 06:00 MHDA- 2019/02/26 06:00 PMCR- 2018/11/14 CRDT- 2018/11/16 06:00 PHST- 2017/11/23 00:00 [received] PHST- 2018/11/09 00:00 [accepted] PHST- 2018/11/16 06:00 [pubmed] PHST- 2019/02/26 06:00 [medline] PHST- 2018/11/16 06:00 [entrez] PHST- 2018/11/14 00:00 [pmc-release] AID - 10.1007/s00262-018-2274-1 [pii] AID - 2274 [pii] AID - 10.1007/s00262-018-2274-1 [doi] PST - ppublish SO - Cancer Immunol Immunother. 2019 Feb;68(2):331-340. doi: 10.1007/s00262-018-2274-1. Epub 2018 Nov 14.