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CAR-T cells secreting BiTEs circumvent antigen escape without detectable toxicity.

Nat Biotechnol. 2019-07; 
ChoiBryan D,YuXiaoling,CastanoAna P,BouffardAmanda A,SchmidtsAndrea,LarsonRebecca C,BaileyStefanie R,BoroughsAngela C,FrigaultMatthew J,LeickMark B,ScarfòIrene,CetruloCurtis L,DemehriShadmehr,NahedBrian V,CahillDaniel P,WakimotoHiroaki,CurryWilliam T,CarterBob S,MausMarce
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Proteins, Expression, Isolation and Analysis Protein concentrations of cell-free, BiTE-containing solutions were determined using the His Tag ELISA Detection Kit (GenScript). Get A Quote

摘要

Chimeric antigen receptor (CAR)-T-cell therapy for solid tumors is limited due to heterogeneous target antigen expression and outgrowth of tumors lacking the antigen targeted by CAR-T cells directed against single antigens. Here, we developed a bicistronic construct to drive expression of a CAR specific for EGFRvIII, a glioblastoma-specific tumor antigen, and a bispecific T-cell engager (BiTE) against EGFR, an antigen frequently overexpressed in glioblastoma but also expressed in normal tissues. CART.BiTE cells secreted EGFR-specific BiTEs that redirect CAR-T cells and recruit untransduced bystander T cells against wild-type EGFR. EGFRvIII-specific CAR-T cells were unable to completely treat tumors with... More

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