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Decade-long WT1-specific CTLs induced by WT1 peptide vaccination

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International Journal of Hematology Aims and scope Submit manuscript

Abstract

Introduction

The peptide-based cancer vaccine targeting Wilms’ tumor 1 (WT1) is a promising immunotherapeutic strategy for hematological malignancies. It remains unclear how long and to what extent the WT1-specific CD8 + cytotoxic T cell (CTL) persist after WT1 peptide vaccination.

Methods

The WT1 peptide vaccine was administered with written consent to a patient with CML in the chronic phase who did not respond well to imatinib, and the patient was followed for 12 years after vaccination. Immune monitoring was performed by specific amplification of WT1-specific CTLs using a mixed lymphocyte peptide culture. T-cell receptors (TCRs) of amplified WT1-specific CTLs were analyzed using next-generation sequencing. This study was approved by the Institutional Review Board of our institution.

Result

WT1-specific CTLs, which were initially detected during WT1 peptide vaccination, persisted at a frequency of less than 5 cells per 1,000,000 CD8 + T cells for more than 10 years. TCR repertoire analysis confirmed the diversity of WT1-specific CTLs 11 years after vaccination. CTLs exhibited WT1 peptide-specific cytotoxicity in vitro.

Conclusion

The WT1 peptide vaccine induced an immune response that persists for more than 10 years, even after cessation of vaccination in the CML patient.

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Data availability

The data that support the findings of this study are available from the corresponding author, M.M., upon reasonable request.

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Acknowledgements

The present study was supported in part by JSPS KAKENHI Grant Number JP17K09006 to Y.S., JP18K07410 to M.N., and JP16K09868 to M.M. and a Japanese Society of Hematology Research Grant (2019–2020) to M.M.

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Authors and Affiliations

  1. Department of Hematopoietic Stem Cell Transplantation, Niigata University Medical and Dental Hospital, Niigata, Japan

    Tatsuya Suwabe & Masayoshi Masuko

  2. Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine, 1-754 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan

    Yasuhiko Shibasaki, Suguru Tamura, Takayuki Katagiri, Kyoko Fuse, Tori Ida-Kurasaki & Hirohito Sone

  3. Laboratory of Hematology and Oncology, Graduate School of Health Sciences, Niigata University, Niigata, Japan

    Takashi Ushiki & Miwako Narita

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  1. Tatsuya Suwabe
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Contributions

TS, MN, and MM designed the present study, conducted all experiments, analyzed the data obtained, and wrote the manuscript. TS and MN performed the MLPC assay. HS supervised this work. All authors discussed the results and contributed to the final manuscript.

Corresponding author

Correspondence to Masayoshi Masuko.

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Suwabe, T., Shibasaki, Y., Tamura, S. et al. Decade-long WT1-specific CTLs induced by WT1 peptide vaccination. Int J Hematol 119, 399–406 (2024). https://doi.org/10.1007/s12185-024-03723-1

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  • DOI: https://doi.org/10.1007/s12185-024-03723-1

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