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
The fundamental advantages of carbon-based graphene material,such as its high tunnelling probability,symmetric band structure(linear dependence of the energy band on the wave direction),low effective mass,and characte...The fundamental advantages of carbon-based graphene material,such as its high tunnelling probability,symmetric band structure(linear dependence of the energy band on the wave direction),low effective mass,and characteristics of its 2D atomic layers,are the main focus of this research work.The impact of channel thickness,gate under-lap,asymmetric source/drain doping method,workfunction of gate contact,and High-K material on Graphene-based Tunnel Field Effect Transistor(TFET)is analyzed with 20 nm technology.Physical modelling and electrical characteristic performance have been simulated using the Atlas device simulator of SILVACO TCAD with user-defined material syntax for the newly included graphene material in comparison to silicon carbide(SiC).The simulation results in significant suppression of ambipolar current to voltage characteristics of TFET and modelled device exhibits a significant improvement in subthreshold swing(0.0159 V/decade),the ratio of Ion/Ioff(1000),and threshold voltage(-0.2 V with highly doped p-type source and 0.2 V with highly doped n-type drain)with power supply of 0.5 V,which make it useful for low power digital applications.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The fundamental advantages of carbon-based graphene material,such as its high tunnelling probability,symmetric band structure(linear dependence of the energy band on the wave direction),low effective mass,and characteristics of its 2D atomic layers,are the main focus of this research work.The impact of channel thickness,gate under-lap,asymmetric source/drain doping method,workfunction of gate contact,and High-K material on Graphene-based Tunnel Field Effect Transistor(TFET)is analyzed with 20 nm technology.Physical modelling and electrical characteristic performance have been simulated using the Atlas device simulator of SILVACO TCAD with user-defined material syntax for the newly included graphene material in comparison to silicon carbide(SiC).The simulation results in significant suppression of ambipolar current to voltage characteristics of TFET and modelled device exhibits a significant improvement in subthreshold swing(0.0159 V/decade),the ratio of Ion/Ioff(1000),and threshold voltage(-0.2 V with highly doped p-type source and 0.2 V with highly doped n-type drain)with power supply of 0.5 V,which make it useful for low power digital applications.
