The Study of Improving Efficiency of Lentivirus Infection in Human γδ T Cells with Small Molecular Drugs
γδ T cells can recognize antigens on target cells independently of major histocompatibility complex(MHC),kill target cells effectively without causing graft versus host disease(GvHD),which has great application prospect in allogenic CAR cell therapy development as platform.Lentivirus vector is a common gene delivery approach in CAR-T cells manufacture.To achieve efficient gene delivery based on lentivirus vector in γδ T cells,this study explored small molecule drugs that can improve lentivirus titer and lentivirus transduction efficiency in γδ T cells.The results showed that histone deacetylase inhibitor M344 and microtubule inhibitor Nocodazole could effectively improve lentivirus titer.Lentivirus titer was increased to more than 2 times with 0.625 μmol/L M344 treatment.TBK1/IKK epsilon inhibitor BX-795 increased the efficiency of lentivirus transduction in γδ T cells,which raised from 3.5％to 10％when multiplicity of infection(MOI)was 5 without causing toxic effects on γδ T cells.This study provides a new strategy for optimizing gene delivery based on lentivirus vector in γδ T cells,and further promotes the application of γδ T cells in allogenic CAR cells therapy.
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