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Exploring the therapeutic potential of precision T-Cell Receptors (TCRs) in targeting KRAS G12D cancer through in vitro development

WEITAO ZHENG1, DONG JIANG2, SONGEN CHEN1, MEILING WU1, BAOQI YAN2, JIAHUI ZHAI2, YUNQIANG SHI2, BIN XIE1, XINGWANG XIE2, KANGHONG HU1,*, WENXUE MA3,*

1 Sino-German Biomedical Center, National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education of China & Hubei Province), Hubei University of Technology, Wuhan, 430068, China
2 Center of Research & Development, Beijing CorreGene Biotechnology Co., Ltd., Beijing, 102206, China
3 Department of Medicine, Sanford Stem Cell Institute and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA

* Corresponding Authors: KANGHONG HU. Email: email; WENXUE MA. Email: email

(This article belongs to the Special Issue: Advances in Cancer Immunotherapy)

Oncology Research 2024, 32(12), 1837-1850. https://doi.org/10.32604/or.2024.056565

Abstract

Objectives: The Kirsten rat sarcoma virus (KRAS) G12D oncogenic mutation poses a significant challenge in treating solid tumors due to the lack of specific and effective therapeutic interventions. This study aims to explore innovative approaches in T cell receptor (TCR) engineering and characterization to target the KRAS G12D7-16 mutation, providing potential strategies for overcoming this therapeutic challenge. Methods: In this innovative study, we engineered and characterized two T cell receptors (TCRs), KDA11-01 and KDA11-02 with high affinity for the KRAS G12D7-16 mutation. These TCRs were isolated from tumor-infiltrating lymphocytes (TILs) derived from tumor tissues of patients with the KRAS G12D mutation. We assessed their specificity and anti-tumor activity in vitro using various cancer cell lines. Results: KDA11-01 and KDA11-02 demonstrated exceptional specificity for the HLA-A*11:01-restricted KRAS G12D7-16 epitope, significantly inducing IFN-γ release and eliminating tumor cells without cross-reactivity or alloreactivity. Conclusions: The successful development of KDA11-01 and KDA11-02 introduces a novel and precise TCR-based therapeutic strategy against KRAS G12D mutation, showing potential for significant advancements in cancer immunotherapy.

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APA Style
ZHENG, W., JIANG, D., CHEN, S., WU, M., YAN, B. et al. (2024). Exploring the therapeutic potential of precision t-cell receptors (tcrs) in targeting KRAS G12D cancer through in vitro development. Oncology Research, 32(12), 1837-1850. https://doi.org/10.32604/or.2024.056565
Vancouver Style
ZHENG W, JIANG D, CHEN S, WU M, YAN B, ZHAI J, et al. Exploring the therapeutic potential of precision t-cell receptors (tcrs) in targeting KRAS G12D cancer through in vitro development. Oncol Res. 2024;32(12):1837-1850 https://doi.org/10.32604/or.2024.056565
IEEE Style
W. ZHENG et al., “Exploring the therapeutic potential of precision T-Cell Receptors (TCRs) in targeting KRAS G12D cancer through in vitro development,” Oncol. Res., vol. 32, no. 12, pp. 1837-1850, 2024. https://doi.org/10.32604/or.2024.056565



cc Copyright © 2024 The Author(s). Published by Tech Science Press.
This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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