WT1 peptide vaccine for the treatment of malignancies: Its development, recent progress, and future perspectives

Abstract

Wilms' tumor gene (WT1) possesses oncogenic functions and is expressed in various hematological malignancies and solid cancers, and the gene product WT1 protein is highly immunogenic, which indicates that WT1 should be a promising target antigen for cancer immunotherapy. The identification of human WT1 cytotoxic T lymphocyte (CTL) epitopes and the demonstration using a mouse model that WT1 could serve in vivo as a target antigen for cancer immunotherapy were reported in 2000. Based on these findings, clinical trials for WT1 peptide vaccine were started. The early clinical trials demonstrated that the WT1 peptide vaccination could induce WT1-specific immunological response such as an increase in WT1-specific CTL frequency, resulting in occurrence of clinical response such as a decrease in leukemia/solid tumor load, which strongly suggested the therapeutic potential of the WT1 peptide vaccine for the treatment of malignancies. A review article published in 2009 in a prestigious journal gave WT1 the highest ranking as a target antigen for cancer immunotherapy. Now, cases which showed immunological and/or clinical responses with treatment by WT1 peptide vaccine are being accumulated. Some of the recent clinical trials showed noteworthy results, such as the demonstration that WT1 peptide vaccination may lead acute myeloid leukemia patients with minimal residual disease to a cure and that the vaccination may prevent relapse of patients with hematological malignancies who have received allogeneic hematopoietic stem cell transplantation but are at high risk of relapse. In addition, clinical usefulness of the WT1 peptide vaccine combined with chemotherapy drugs or molecular target-based drugs was also suggested. Continuing progress of WT1-targeting immunotherapy, a translational research based on basic research, should lead to innovative development of cancer immunotherapy. Furthermore, comprehensive analysis of the samples obtained from the patients treated with the WT1-targeting immunotherapy, a reverse-translational research, should contribute to the elucidation of cancer immunity mechanisms.