A phase I clinical study of a cocktail vaccine of Wilms’ tumor 1 (WT1) HLA class I and II peptides for recurrent malignant glioma

• Published in: Cancer Immunology, Immunotherapy Vol. 68; no. 2; pp. 331 - 340
• Main Authors: Tsuboi, Akihiro, Hashimoto, Naoya, Fujiki, Fumihiro, Morimoto, Soyoko, Kagawa, Naoki, Nakajima, Hiroko, Hosen, Naoki, Nishida, Sumiyuki, Nakata, Jun, Morita, Satoshi, Sakamoto, Junichi, Oji, Yusuke, Oka, Yoshihiro, Sugiyama, Haruo
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2019; Springer Nature B.V
• Subjects: Adult; Brain Neoplasms - drug therapy; Brain Neoplasms - immunology; Brain Neoplasms - pathology; Cancer Research; Cancer vaccines; Cancer Vaccines - immunology; Cancer Vaccines - therapeutic use; Clinical Trial Report; Female; Glioma; Glioma - drug therapy; Glioma - immunology; Glioma - pathology; Histocompatibility antigen HLA; Histocompatibility Antigens Class II - immunology; HLA-A24 Antigen - immunology; Humans; Immunology; Immunotherapy; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Recurrence, Local; Oncology; Peptides; Safety; Survival Analysis; Toxicity; Treatment Outcome; Vaccination; Vaccination - methods; Vaccines; Vaccines, Subunit - immunology; Vaccines, Subunit - therapeutic use; WT1 Proteins - immunology; Malignant glioma; Cancer vaccine; Peptide vaccine; Cancer immunotherapy; HLA class II peptide; WT1
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-018-2274-1

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.