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...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-γrelease 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.展开更多
本文回顾性分析2021年3月山东大学附属威海市立医院收治的1例CD4^(-)CD8^(-)TCRγδ^(+)T细胞大颗粒淋巴细胞白血病(T-cell large granular lymphocyte leukemia,T-LGLL)合并纯红细胞再生障碍性贫血(Pure red cell aplasia,PRCA)患者的...本文回顾性分析2021年3月山东大学附属威海市立医院收治的1例CD4^(-)CD8^(-)TCRγδ^(+)T细胞大颗粒淋巴细胞白血病(T-cell large granular lymphocyte leukemia,T-LGLL)合并纯红细胞再生障碍性贫血(Pure red cell aplasia,PRCA)患者的临床资料,并复习相关文献,以提高对CD4^(-)CD8^(-)TCRγδ^(+)T-LGLL合并PRCA的认知,从而减少临床中的误诊及漏诊。展开更多
基金funded by the key R&D Project of Hubei Province(Social Development),China(2022BCA018)the Cooperative Innovation Center of Industrial Fermentation(Ministry of Education&Hubei Province),China(2022KF16)to Kanghong Hu.
文摘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-γrelease 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.
文摘本文回顾性分析2021年3月山东大学附属威海市立医院收治的1例CD4^(-)CD8^(-)TCRγδ^(+)T细胞大颗粒淋巴细胞白血病(T-cell large granular lymphocyte leukemia,T-LGLL)合并纯红细胞再生障碍性贫血(Pure red cell aplasia,PRCA)患者的临床资料,并复习相关文献,以提高对CD4^(-)CD8^(-)TCRγδ^(+)T-LGLL合并PRCA的认知,从而减少临床中的误诊及漏诊。
