Anti-Cancer Potential of Transiently Transfected HER2-Specific Human Mixed CAR-T and NK Cell Populations in Experimental Models: Initial Studies on Fucosylated Chondroitin Sulfate Usage for Safer Treatment

Anti-Cancer Potential of Transiently Transfected HER2-Specific Human Mixed CAR-T and NK Cell Populations in Experimental Models: Initial Studies on Fucosylated Chondroitin Sulfate Usage for Safer Treatment

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Human epidermal growth factor receptor 2 (HER2) is overexpressed in numerous cancer cell types.Therapeutic antibodies and chimeric antigen receptors (CARs) against HER2 were developed to treat human tumors.The major limitation of anti-HER2 CAR-T lymphocyte therapy is attributable to the low HER2 expression in a wide range of normal tissues.

Thus, side effects are caused by CAR lymphocyte “on-target off-tumor” reactions.We aimed to develop safer HER2-targeting CAR-based therapy.CAR constructs against HER2 tumor-associated antigen (TAA) for transient expression were delivered into target T and Drone natural killer (NK) cells by an effective and safe non-viral transfection method via nucleofection, excluding the risk of mutations associated with viral transduction.

Different in vitro end-point and real-time assays of the CAR lymphocyte antitumor cytotoxicity and in vivo human HER2-positive tumor xenograft mice model proved potent Armored Vehicle cytotoxic activity of the generated CAR-T-NK cells.Our data suggest transient expression of anti-HER2 CARs in plasmid vectors by human lymphocytes as a safer treatment for HER2-positive human cancers.We also conducted preliminary investigations to elucidate if fucosylated chondroitin sulfate may be used as a possible agent to decrease excessive cytokine production without negative impact on the CAR lymphocyte antitumor effect.