WT1 Trio Peptide-Based Cancer Vaccine for Rare Cancers Expressing Shared Target WT1

Abstract

No standard treatment has been established for most rare cancers. Here, we report a clinical trial of a biweekly WT1 tri-peptide-based vaccine for recurrent or advanced rare cancers. Due to the insufficient number of patients available for a traditional clinical trial, the trial was designed for rare cancers expressing shared target molecule WT1. The recruitment criteria included WT1-expressing tumors as well as HLA-A*24:02 or 02:01. The primary endpoints were immunoglobulin G (IgG) antibody (Ab) production against the WT1-235 cytotoxic T lymphocyte (CTL) epitope and delayed-type hypersensitivity (DTH) skin reactions to targeted WT1 CTL epitopes. The secondary endpoints were safety and clinical efficacy. Forty-five patients received WT1 Trio, and 25 (55.6%) completed the 3-month protocol treatment. WT1-235 IgG Ab was positive in 88.0% of patients treated with WT1 Trio at 3 months, significantly higher than 62.5% of the weekly WT1-235 CTL peptide vaccine. The DTH positivity rate in WT1 Trio was 62.9%, which was not significantly different from 60.7% in the WT1-235 CTL peptide vaccine. The WT1 Trio safety was confirmed without severe treatment-related adverse events, except grade 3 myasthenia gravis-like symptoms observed in a patient with thymic cancer. Fifteen (33.3%) patients achieved stable disease after 3 months of treatment. In conclusion, the biweekly WT1 Trio vaccine containing the WT1-332 helper T lymphocyte peptide induced more robust immune responses targeting WT1 than the weekly WT1-235 CTL peptide vaccine. Therefore, WT1-targeted immunotherapy may be a potential therapeutic strategy for rare cancers.

Wilms’ tumor 1 -targeting cancer vaccine: Recent advancements and future perspectives

“… Author Phase n Vaccine type Disease Clinical outcome Immune response Note Nishida 8 2 (randomized) 91 CTL peptide vaccine +GEM vs GEM Pancreatic cancer 1-year OS (35.7% vs 20.9%) PFS extension, (HR, 0.66) WT1 vaccine combined with GEM prolonged PFS and 1-year OS Nishida 11 2 25 CTL peptide Ovarian cancer Longer PFS: WT1-specific CTL and IgG level are prognostic makers for WT1 vaccine % tetramer-high CTL≧0.25% or WT1-235 IgG ≧0.1 U/ml Oji 12 2 15 CTL peptide Thymic epithelial Cancer No CR and PR,SD: 75% WT1-specific immune response in majority of patients WT1 vaccine showed antitumor potential against thymic malignancies. Tsuboi 15 1 14 CTL+ helper peptide Malignant glioma SD: 43%, 1-year OS: 36%, mOS: 24.7 weeks Promising outcomes for patients with malignant glioma Oji 16 2 45 CTL+ helper peptide Rare cancers SD: 33.3% at 3 months WT1-235 IgG positivity: 88% WT1 CTL+helper peptide vaccine induced robust immune responses against WT1in patients with rare cancers. …”

“…Oji et al conducted a clinical trial where they administered the WT1 CTL peptide (WT1-235) along with a helper peptide (WT1–332) to 45 patients with rare cancers such as glioblastoma multiforme, soft-tissue cancer, thymic cancer, and malignant pleural mesothelioma, all expressing WT1. 16 They monitored the titers of WT1-specific IgG antibodies against each peptide over time. After vaccine administration, they observed an increase in antibody titers.…”

New Horizons in Immunology and Immunotherapy of Acute Leukemias and Related Disorders

“…In the first paper included, published by Yusuke Oji [14], a promising novel immunotherapeutic tool was proposed. It was based on a WT1 trio peptide-based cancer vaccine for rare cancers expressing the shared target WT1.…”