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

Autor: Oji Y; Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Kagawa N; Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Arita H; Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.; Department of Neurosurgery, Osaka International Cancer Institute, Osaka 541-8567, Japan., Naka N; Department of Orthopedic Surgery, Nachikatsuura Town Onsen Hospital, Nachikatsuura, Wakayama 649-5331, Japan., Hamada KI; Hamada Orthopedic Surgery, Kawanishi City 666-0021, Japan., Outani H; Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Shintani Y; Department of Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Takeda Y; Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Morii E; Department of Pathology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Shimazu K; Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Suzuki M; Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Nishida S; Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.; Strategic Global Partnership & X-Innovation Initiative Graduate School of Medicine, Osaka University & Osaka University Hospital, Osaka 565-0871, Japan., Nakata J; Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Tsuboi A; Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Iwai M; Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Hayashi S; Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Imanishi R; Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Ikejima S; Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Kanegae M; Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Iwamoto M; Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Ikeda M; Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Yagi K; Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Shimokado H; Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Nakajima H; Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Hasegawa K; Laboratory of Cellular Immunotherapy, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan., Morimoto S; Department of Cancer Stem Cell biology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Fujiki F; Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Nagahara A; Department of Urology, Osaka International Cancer Institute, Osaka 541-8567, Japan., Tanemura A; Department of Dermatology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Ueda Y; Department of Gynecology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Mizushima T; Department of Surgery, Osaka Police Hospital, Osaka 543-0035, Japan., Ohmi M; Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Ishida T; Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Fujimoto M; Department of Dermatology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Nonomura N; Department of Urology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Kimura T; Department of Gynecology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Inohara H; Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Okada S; Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Kishima H; Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Hosen N; Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Kumanogoh A; Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Oka Y; Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.; Department of Cancer Stem Cell biology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Sugiyama H; Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2023 Jan 06; Vol. 15 (2). Date of Electronic Publication: 2023 Jan 06.
DOI: 10.3390/cancers15020393
Abstrakt: 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.
Databáze: MEDLINE
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