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

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.

Influence of construction-induced damage on the degradation of freeze—thawed lightweight cellular concrete

During the construction of lightweight cellular concrete(LCC),material damage frequently occurs,causing the degradation and deterioration of the mechanical performance,durability,and subgrade quality of LCC.The construction-induced damage can be more significant than those from the service environment of LCC,such as freeze-thaw(F-T)action in cold regions.However,the effect of construction-induced damage on LCC during F-T cycles is often ignored and the deterioration mechanisms are not yet clarified.In this study,we investigated the factors causing damage during construction using a sample preparation method established to simulate the damage in the laboratory setting.We conducted F-T cycle tests and microstructural characterization to study the effect of microstructural damage on the overall strength of LCC with different water contents under F-T actions.We established the relationship between the pore-area ratio and F-T cycle times,pore-area ratio,and strength,as well as the F-T cycle times and strength under different damage forms.The damage evolution is provided with the rationality of the damage equation,verified by comparing the measured and predicted damage variables.This study would serve as a guide for the construction and performance of LCC in cold regions.

Quality evaluation of lightweight cellular concrete by an ultrasound-based method

The accuracy of subgrade quality evaluation is important for road safety assessment.Since there is little research work devoted to testing lightweight cellular concrete(LCC)by an ultrasound-based method,the quantitative relation between ultrasonic testing results and the quality of LCC subgrade is not well understood.In this paper,the quality of LCC subgrade was evaluated with respect to compressive strength and crack discrimination.The relation between ultrasonic testing results and LCC quality was explored through indoor tests.Based on the quantitative relation between ultrasonic pulse velocity and compressive strength of LCC,a fitting formula was established.Moreover,after the LCC became cracked,the ultrasonic pulse velocity and ultrasonic pulse amplitude decreased.After determining the lower limiting values of the ultrasonic pulse velocity and ultrasonic pulse amplitude through the statistical data,it could be calculated whether there were cracks in LCC subgrade.The ultrasonic testing results showed that the compressive strength of the LCC subgrade was suitable for purpose and there was no crack in the subgrade.Then core samples were taken from the subgrade.Comparisons between ultrasonic testing results of subgrade and test results of core samples demonstrated a good agreement.