In situ tumor cell engineering reverses immune escape to enhance immunotherapy effect

》》文章原文链接：In situ tumor cell engineering reverses immune escape to enhance immunotherapy effect

》》Journal：Acta Pharm. Sin. B.

》》相关产品：Hoechst 33342 (SJ-MD0033)

》》产品引用描述：

》》Abstract

The underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an in situ tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL+ B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared. LCPN@ACD-induced ICD promoted DC maturation and enhanced T-cell activation and infiltration. LCPN@ACD enabled effective expression of MHC-I/TSA on tumor cells, increasing the ability of tumor cell recognition and killing. LCPN@ACD downregulated tumor cell CD55 expression, increased the proportion of ICOSL+ B cells and CTLs, and reversed the TIME, thus greatly improving the efficacy of αPD-1 and CAR-T therapies. The application of this in situ tumor cell engineering strategy eliminated the source of tumor immune escape, providing new ideas for solving the challenges of clinical immunotherapy.

》》部分文献数据展示：

Fig. 3. (H) Quantified fluorescence intensity of tumor sphere slices. Representative image and fluorescence distribution of AF488-pDNA and lysosome in MC38 cells after incubated with AF488-pDNA and LCPN-AF488 (pH=6.5) for 2 h (I and J) and 5 h (K and L), scale bar = 30 μm. Lysosome was labeled in red, AF488-pDNA was in green. Line in red represent the fluorescent intensity of lysosome, line in green represent the fluorescent intensity of AF488-pDNA. LNP@ACD represents drug loaded inner lipid nanoparticle;