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

Cancer Immunol Immunother. 2019 Feb;68(2):331-340. doi: 10.1007/s00262-018-2274-1. Epub 2018 Nov 14.

Abstract

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.

Keywords: Cancer immunotherapy; Cancer vaccine; HLA class II peptide; Malignant glioma; Peptide vaccine; WT1.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / immunology
  • Brain Neoplasms / pathology
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Female
  • Glioma / drug therapy*
  • Glioma / immunology
  • Glioma / pathology
  • HLA-A24 Antigen / immunology
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Survival Analysis
  • Treatment Outcome
  • Vaccination / methods
  • Vaccines, Subunit / immunology
  • Vaccines, Subunit / therapeutic use*
  • WT1 Proteins / immunology

Substances

  • Cancer Vaccines
  • HLA-A*24:02 antigen
  • HLA-A24 Antigen
  • Histocompatibility Antigens Class II
  • Vaccines, Subunit
  • WT1 Proteins