Cancers (Jan 2023)
WT1 Trio Peptide-Based Cancer Vaccine for Rare Cancers Expressing Shared Target WT1
- Yusuke Oji,
- Naoki Kagawa,
- Hideyuki Arita,
- Norifumi Naka,
- Ken-ichiro Hamada,
- Hidetatsu Outani,
- Yasushi Shintani,
- Yoshito Takeda,
- Eiichi Morii,
- Kenzo Shimazu,
- Motoyuki Suzuki,
- Sumiyuki Nishida,
- Jun Nakata,
- Akihiro Tsuboi,
- Miki Iwai,
- Sae Hayashi,
- Rin Imanishi,
- Sayaka Ikejima,
- Mizuki Kanegae,
- Masahiro Iwamoto,
- Mayu Ikeda,
- Kento Yagi,
- Haruka Shimokado,
- Hiroko Nakajima,
- Kana Hasegawa,
- Soyoko Morimoto,
- Fumihiro Fujiki,
- Akira Nagahara,
- Atsushi Tanemura,
- Yutaka Ueda,
- Tsunekazu Mizushima,
- Masato Ohmi,
- Takayuki Ishida,
- Manabu Fujimoto,
- Norio Nonomura,
- Tadashi Kimura,
- Hidenori Inohara,
- Seiji Okada,
- Haruhiko Kishima,
- Naoki Hosen,
- Atsushi Kumanogoh,
- Yoshihiro Oka,
- Haruo Sugiyama
Affiliations
- Yusuke Oji
- Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Naoki Kagawa
- Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Hideyuki Arita
- Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Norifumi Naka
- Department of Orthopedic Surgery, Nachikatsuura Town Onsen Hospital, Nachikatsuura, Wakayama 649-5331, Japan
- Ken-ichiro Hamada
- Hamada Orthopedic Surgery, Kawanishi City 666-0021, Japan
- Hidetatsu Outani
- Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Yasushi Shintani
- Department of Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Yoshito Takeda
- Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Eiichi Morii
- Department of Pathology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Kenzo Shimazu
- Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Motoyuki Suzuki
- Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Sumiyuki Nishida
- Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Jun Nakata
- Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Akihiro Tsuboi
- Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Miki Iwai
- Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Sae Hayashi
- Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Rin Imanishi
- Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Sayaka Ikejima
- Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Mizuki Kanegae
- Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Masahiro Iwamoto
- Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Mayu Ikeda
- Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Kento Yagi
- Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Haruka Shimokado
- Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Hiroko Nakajima
- Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Kana Hasegawa
- Laboratory of Cellular Immunotherapy, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
- Soyoko Morimoto
- Department of Cancer Stem Cell biology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Fumihiro Fujiki
- Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Akira Nagahara
- Department of Urology, Osaka International Cancer Institute, Osaka 541-8567, Japan
- Atsushi Tanemura
- Department of Dermatology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Yutaka Ueda
- Department of Gynecology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Tsunekazu Mizushima
- Department of Surgery, Osaka Police Hospital, Osaka 543-0035, Japan
- Masato Ohmi
- Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Takayuki Ishida
- Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Manabu Fujimoto
- Department of Dermatology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Norio Nonomura
- Department of Urology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Tadashi Kimura
- Department of Gynecology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Hidenori Inohara
- Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Seiji Okada
- Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Haruhiko Kishima
- Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Naoki Hosen
- Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Atsushi Kumanogoh
- Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Yoshihiro Oka
- Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- Haruo Sugiyama
- Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- DOI
- https://doi.org/10.3390/cancers15020393
- Journal volume & issue
-
Vol. 15,
no. 2
p. 393
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.
Keywords
