@article{ZHENG2024, 
author = {WEITAO ZHENG and DONG JIANG and SONGEN CHEN and MEILING WU and BAOQI YAN and JIAHUI ZHAI and YUNQIANG SHI and BIN XIE and XINGWANG XIE and KANGHONG HU and WENXUE MA},
title = {Exploring the therapeutic potential of precision T-Cell Receptors (TCRs) in targeting KRAS G12D cancer through in vitro development},
year = {2024},
journal = {Oncology Research},
volume = {32},
number = {12},
pages = {1837-1850},
keywords = {T cell receptor (TCR), TCR therapy, Tumor-infiltrating lymphocytes (TILs), Kirsten rat sarcoma virus (KRAS), G12D, Alloreactivity},
url = {https://www.sciopen.com/article/10.32604/or.2024.056565},
doi = {10.32604/or.2024.056565},
abstract = {ObjectivesThe 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.MethodsIn 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.ResultsKDA11-01 and KDA11-02 demonstrated exceptional specificity for the HLA-A*:01-restricted KRAS G12D7-16 epitope, significantly inducing IFN-γ release and eliminating tumor cells without cross-reactivity or alloreactivity.ConclusionsThe 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.}
}