WT1 Trio Peptide-Based Cancer Vaccine for Rare Cancers Expressing Shared Target WT1
Yusuke Oji1, Naoki Kagawa2, Hideyuki Arita2,3
1Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
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.
Insights
A novel biweekly WT1 tri-peptide vaccine (WT1 Trio) demonstrated enhanced immune responses in rare cancer patients. This WT1-targeted immunotherapy shows potential as a new treatment strategy for these challenging diseases.
Area of Science:
- Immunology
- Oncology
- Vaccinology
Background:
- Standard treatments for rare cancers are lacking.
- The Wilms' Tumor 1 (WT1) antigen is a shared target in various rare cancers.
- Clinical trials for rare cancers are challenging due to small patient populations.
Purpose of the Study:
- To evaluate the safety and efficacy of a biweekly WT1 tri-peptide-based vaccine (WT1 Trio) in patients with recurrent or advanced rare cancers.
- To compare the immunogenicity of WT1 Trio against a weekly WT1-235 CTL peptide vaccine.
- To assess clinical outcomes including antibody production, skin reactions, and disease progression.
Main Methods:
- A clinical trial involving 45 patients with WT1-expressing rare cancers and specific HLA types (HLA-A*24:02 or 02:01).
- Patients received the biweekly WT1 Trio vaccine.
- Primary endpoints included immunoglobulin G (IgG) antibody production and delayed-type hypersensitivity (DTH) reactions.
- Secondary endpoints focused on safety and clinical efficacy.
Main Results:
- WT1 Trio induced a significantly higher IgG antibody response (88.0%) compared to the weekly vaccine (62.5%).
- DTH positivity rates were comparable between WT1 Trio (62.9%) and the weekly vaccine (60.7%).
- The vaccine was generally safe, with one case of severe myasthenia gravis-like symptoms.
- Stable disease was achieved in 33.3% of patients after 3 months.
Conclusions:
- The biweekly WT1 Trio vaccine, incorporating a WT1 helper T lymphocyte peptide, elicits a more robust immune response targeting WT1 than the weekly CTL peptide vaccine.
- WT1-targeted immunotherapy represents a promising therapeutic avenue for rare cancers.
- The study highlights the potential of shared antigen-targeted vaccines in overcoming challenges in rare cancer clinical trials.
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