IMCT-09WT1 PEPTIDE VACCINATION FOR GLIOMAS; SURVIVALS, BIOMARKERS AND RESPONSE ASSESSMENT

Abstract

We have completed two clinical trials on WT1 peptide vaccination against gliomas; phase II trial for recurrent ones (Izumoto, Hashimoto et al., J Neurosurg, 2008) and phase I trial for newly diagnosed glioblastomas focusing on the safe combination with temozolomide (Hashimoto et al., Cancer Immunol Immunother, 2015). Although patients' survival data have been shown in the past SNO meetings, recently updated data for longer follow-up period will be presented. Especially, WT1 vaccination combined with Stupp regimen in the latter trial against glioblastomas produced progression free survival over 48 months in 5 of 7 patients recruited. Subsequent analyses from those trials revealed some immunological and non-immunological biomarkers on response to the vaccination. High level of WT1 protein and HLA class I expression on tumor cells were predictive of longer survival. Immunologically, increased WT1-specific T cells and WT1 antibody in peripheral blood after the vaccination were also predictive, and positive change of delayed type hypersensitivity (DTH) within 3 months from the start of vaccination was also a biomarker; those should rather be thought as “proof of concept” of this immunotherapy. Samples from 20 non-responders who required surgical intervention after vaccination revealed that tumor cells might have escaped from immunological attack by decreasing WT1 and HLA expression, by comparing with pre-vaccination samples in the same patients. On the response assessment, we reported that methionine PET was more accurate than enhancing MRI, when assuming survivals (Chiba, Hashimoto et al., J Neurosurg, 2012). Among MRI-based response assessments of RECIST, Macdonald, immune-related response criteria (irRC) and RANO, our analyses using 60 patients have revealed that RANO was the most appropriate surrogate of survivals in early phase, although more accurate criteria specific to immunotherapy on brain tumors were warranted.