2. Academic Validation
  3. Identification of mouse helper epitopes for WT1-specific CD4+ T cells

Identification of mouse helper epitopes for WT1-specific CD4+ T cells

  • Cancer Immunol Immunother. 2021 Nov;70(11):3323-3335. doi: 10.1007/s00262-021-03003-5.
Hiroko Nakajima 1,  Jun Nakata 2,  Kanako Imafuku 2,  Hiromu Hayashibara 2,  Kazuki Isokawa 2,  Keiko Udaka 3,  Fumihiro Fujiki 4,  Soyoko Morimoto 5,  Kana Hasegawa 4,  Naoki Hosen 6,  Yoshiko Hashii 5,  Sumiyuki Nishida 7,  Akihiro Tsuboi 5,  Yoshihiro Oka 7 8 9,  Yusuke Oji 2,  Shinji Sogo 4 10,  Haruo Sugiyama 4
Affiliations

Affiliations

  • 1 Department of Cancer Immunology, Osaka University Graduate School of Medicine, 1-7 Yamadaoka, Suita-city, Osaka, 565-0871, Japan. hnakaji@cit.med.osaka-u.ac.jp.
  • 2 Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka, Japan.
  • 3 Department of Immunology, School of Medicine, Kochi University, Kochi, Japan.
  • 4 Department of Cancer Immunology, Osaka University Graduate School of Medicine, 1-7 Yamadaoka, Suita-city, Osaka, 565-0871, Japan.
  • 5 Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Osaka, Japan.
  • 6 Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
  • 7 Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.
  • 8 Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan.
  • 9 Department of Immunopathology, WPI, Immunology Frontier Research Center (iFReC), Osaka University, Osaka, Japan.
  • 10 Immunology Research Unit, Department of Medical Innovations, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
PMID: 34272593 DOI: 10.1007/s00262-021-03003-5
Abstract

Helper T lymphocytes (HTLs) play a central role in Cancer immunity because they can not only help the induction and proliferation of cytotoxic T lymphocytes (CTLs) but also their differentiation into cytotoxic CD4+ T cells and directly kill the target cells.This study describes the identification of three novel mouse Th epitope peptides, WT135-52, WT186-102 and WT1294-312, derived from WT1 protein, which is the most potent tumor-associated antigen. Compared to immunization with WT1 CTL peptide alone, immunization with the addition of these WT1-specific Th peptides strongly induced WT1-specific CTLs, continued to maintain them, and efficiently rejected the challenge of WT1-expressing tumor cells. Importantly, the majority of WT1-specific CTLs induced by the co-immunization with WT1 CTL and the WT1-specific Th peptides were CD44+CD62L- effector memory CD8+ T cells, which played a central role in tumor rejection. Establishment of mouse models suitable for the analysis of the detailed mechanism of these functions of HTLs is very important. These results clearly showed that WT1-specific HTLs perform an essential function in WT1-specific tumor immunity. Therefore, the WT1-specific Th peptides identified here should make a major contribution to elucidation of the mutual roles of WT1-specific CTLs and HTLs in Cancer immunity in in vivo mouse models.

Keywords

CTL; HTL; Helper peptide; Peptide vaccine; WT1.

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