Engineered Cell Nanovesicles Overcome Immunotherapy Resistance In HNSCC

In recent years, immune checkpoint inhibitors struggle to overcome the immune evasion mechanisms of tumor cells in some subtypes of head and neck squamous cell carcinoma (HNSCC), so we designed engineered nanovesicles derived from cytokine-induced killer (CIK) cells to overcome this immunotherapy resistance. We designed nanovesicles derived from CIK cells loaded with Doxorubicin (DOX). FasL and TRAIL on the surface directly kill tumor cells by bypassing the immune evasion mechanism of tumor cells. In addition to producing direct killing, DOX causes immunogenic death (ICD) of tumor cells, thereby activating DC cells and initiating downstream adaptive immunity. We induced CIK cells and then obtained DOX@NVs by physical extrusion and co-incubation with DOX. The material characterization experiments included DLS, TEM and CLSM. In vitro experiments included CCK8 cytotoxicity assay, ICD-related index detection and FC to detect BMDC maturation. In vivo, MOC2 cells were used to establish the mouse model in situ, then the tumor volume monitoring and related immune cell FC analysis were performed. 1. The successful preparation of DOX@NVs. 2. In vitro experiment results: DOX@NVs had the strongest ability of killing tumor cells, ICD induction and BMDC maturation promotion. 3. In vivo experiment results: DOX@NVs group had the smallest tumor volume and the strongest activation of immune cells. DOX@NVs overcome the immunotherapy resistance of HNSCC through directly killing tumor cells by bypassing the immune evasion mechanism and subsequent immune activation.