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

被引：5

作者：

Oji, Yusuke ^{[1
]}

Kagawa, Naoki ^{[2
]}

Arita, Hideyuki ^{[2
,3
]}

Naka, Norifumi ^{[4
]}

Hamada, Ken-ichiro ^{[5
]}

Outani, Hidetatsu ^{[6
]}

Shintani, Yasushi ^{[7
]}

Takeda, Yoshito ^{[8
]}

Morii, Eiichi ^{[9
]}

Shimazu, Kenzo ^{[10
]}

Suzuki, Motoyuki ^{[11
]}

Nishida, Sumiyuki ^{[8
,12
,13
]}

Nakata, Jun ^{[1
]}

Tsuboi, Akihiro ^{[14
]}

Iwai, Miki ^{[1
]}

Hayashi, Sae ^{[1
]}

Imanishi, Rin ^{[1
]}

Ikejima, Sayaka ^{[1
]}

Kanegae, Mizuki ^{[1
]}

Iwamoto, Masahiro ^{[1
]}

Ikeda, Mayu ^{[1
]}

Yagi, Kento ^{[1
]}

Shimokado, Haruka ^{[1
]}

Nakajima, Hiroko ^{[15
]}

Hasegawa, Kana ^{[16
]}

Morimoto, Soyoko ^{[17
]}

Fujiki, Fumihiro ^{[14
]}

Nagahara, Akira ^{[18
]}

Tanemura, Atsushi ^{[19
]}

Ueda, Yutaka ^{[20
]}

Mizushima, Tsunekazu ^{[21
]}

Ohmi, Masato ^{[22
]}

Ishida, Takayuki ^{[22
]}

Fujimoto, Manabu ^{[19
]}

Nonomura, Norio ^{[23
]}

Kimura, Tadashi ^{[20
]}

Inohara, Hidenori ^{[11
]}

Okada, Seiji ^{[6
]}

Kishima, Haruhiko ^{[2
]}

Hosen, Naoki ^{[24
]}

Kumanogoh, Atsushi ^{[8
,16
]}

Oka, Yoshihiro ^{[8
,17
]}

Sugiyama, Haruo ^{[15
]}

机构：

[1] Osaka Univ, Dept Clin Lab & Biomed Sci, Grad Sch Med, Suita, Osaka 5650871, Japan

[2] Osaka Univ, Dept Neurosurg, Grad Sch Med, Suita, Osaka 5650871, Japan

[3] Osaka Int Canc Inst, Dept Neurosurg, Osaka 5418567, Japan

[4] Nachikatsuura Town Onsen Hosp, Dept Orthoped Surg, Nachikatsuura, Wakayama 6495331, Japan

[5] Hamada Orthoped Surg, Kawanishi City 6660021, Japan

[6] Osaka Univ, Dept Orthoped Surg, Grad Sch Med, Suita, Osaka 5650871, Japan

[7] Osaka Univ, Dept Thorac Surg, Grad Sch Med, Suita, Osaka 5650871, Japan

[8] Osaka Univ, Dept Resp Med & Clin Immunol, Grad Sch Med, Suita, Osaka 5650871, Japan

[9] Osaka Univ, Dept Pathol, Grad Sch Med, Suita, Osaka 5650871, Japan

[10] Osaka Univ, Dept Breast & Endocrine Surg, Grad Sch Med, Suita, Osaka 5650871, Japan

[11] Osaka Univ, Dept Otorhinolaryngol Head & Neck Surg, Grad Sch Med, Suita, Osaka 5650871, Japan

[12] Osaka Univ, Grad Sch Med, Strateg Global Partnership & X Innovat Initiat, Suita, Osaka 5650871, Japan

[13] Osaka Univ Hosp, Suita, Osaka 5650871, Japan

[14] Osaka Univ, Dept Canc Immunotherapy, Grad Sch Med, Suita, Osaka 5650871, Japan

[15] Osaka Univ, Dept Canc Immunol, Grad Sch Med, Suita, Osaka 5650871, Japan

[16] Osaka Univ, World Premier Int Immunol Frontier Res Ctr, Lab Cellular Immunotherapy, Suita, Osaka 5650871, Japan

[17] Osaka Univ, Dept Canc Stem Cell Biol, Grad Sch Med, Suita, Osaka 5650871, Japan

[18] Osaka Int Canc Inst, Dept Urol, Osaka 5418567, Japan

[19] Osaka Univ, Dept Dermatol, Grad Sch Med, Suita, Osaka 5650871, Japan

[20] Osaka Univ, Dept Gynecol, Grad Sch Med, Suita, Osaka 5650871, Japan

[21] Osaka Police Hosp, Dept Surg, Osaka 5430035, Japan

[22] Osaka Univ, Dept Med Phys & Engn, Grad Sch Med, Suita, Osaka 5650871, Japan

[23] Osaka Univ, Dept Urol, Grad Sch Med, Suita, Osaka 5650871, Japan

[24] Osaka Univ, Dept Hematol & Oncol, Grad Sch Med, Suita, Osaka 5650871, Japan

来源：

CANCERS | 2023年 / 15卷 / 02期

关键词：

rare cancer; WT1; cancer vaccine; TUMOR GENE WT1; TERTIARY LYMPHOID STRUCTURES; CYTOTOXIC T-LYMPHOCYTES; B-CELLS; OVEREXPRESSION; IMMUNOTHERAPY; PROMOTES; SURVIVAL; INDUCTION; IMMUNITY;

D O I：

10.3390/cancers15020393

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Simple Summary Therapeutic options for rare cancers are frequently limited and less effective than for common cancers. Therefore, novel therapeutic strategies to treat rare cancers are urgently required. Our clinical study on rare cancers showed that the biweekly WT1 Trio peptide vaccine comprising two WT1-cytotoxic T lymphocyte (CTL)-peptides and one WT1-helper T lymphocyte-peptide induced more robust immune responses targeting WT1 than the weekly WT1-CTL peptide (WT1-235) vaccine. In addition, the safety of WT1 Trio was confirmed without severe treatment-related adverse events, except grade 3 myasthenia gravis-like symptoms observed in a patient with thymic cancer (TC). Fifteen (33.3%) of the 45 patients with recurrent or advanced rare cancers, including malignant glioma, soft-tissue sarcoma, TC, and malignant pleural mesothelioma, achieved stable disease after 3 months of protocol treatment. Therefore, since WT1 is widely overexpressed in rare cancers, WT1-targeted immunotherapy may be a therapeutic strategy for rare cancers. 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.

引用

页数：18

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