@Article{or.2024.056565,
AUTHOR = {WEITAO ZHENG, DONG JIANG, SONGEN CHEN, MEILING WU, BAOQI YAN, JIAHUI ZHAI, YUNQIANG SHI, BIN XIE, XINGWANG XIE, KANGHONG HU, WENXUE MA},
TITLE = {Exploring the therapeutic potential of precision T-Cell Receptors (TCRs) in targeting KRAS G12D cancer through <i>in vitro</i> development},
JOURNAL = {Oncology Research},
VOLUME = {32},
YEAR = {2024},
NUMBER = {12},
PAGES = {1837--1850},
URL = {http://www.techscience.com/or/v32n12/58616},
ISSN = {1555-3906},
ABSTRACT = { <b>Objectives:</b> 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 G12D<sub>7-16</sub> mutation, providing potential strategies for overcoming this therapeutic challenge. <b>Methods:</b> In this innovative study, we engineered and characterized two T cell receptors (TCRs), KDA11-01 and KDA11-02 with high affinity for the KRAS G12D<sub>7-16</sub> 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 <i>in vitro</i> using various cancer cell lines. <b>Results:</b> KDA11-01 and KDA11-02 demonstrated exceptional specificity for the HLA-A*11:01-restricted KRAS G12D<sub>7-16</sub> epitope, significantly inducing IFN-γ release and eliminating tumor cells without cross-reactivity or alloreactivity. <b>Conclusions:</b> 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.},
DOI = {10.32604/or.2024.056565}
}