CELL INTELLIGENCE · 肿瘤细胞治疗研究

Adoptive cell therapy (ACT) utilizing T cells is becoming a promising option for the treatment of cancer, because it offers an off-the-shelf allogeneic product that is safe, potent, and clinically effective. Approaches to engineer or enhance immune-competent cells for ACT, like expression of chimeric antigen receptors (CARs) or combination treatments with bispecific T cell engagers, have improved the specificity and cytotoxic potential of ACTs and have shown great promise in preclinical and clinical settings. Here, we test whether electroporation of T cells with CAR or secreted bispecific T cell engager (sBite) mRNA is an effective approach to improve the cytotoxicity of T cells. Using a CD19-specific CAR, approximately 60% of T cells are modified after mRNA electroporation and these cells show potent anticancer activity in vitro and in vivo against two CD19-positive cancer cell lines. In addition, expression and secretion of a CD19 sBite enhances T cell cytotoxicity, both in vitro and in vivo , and promotes killing of target cells by modified and unmodified T cells. Taken together, we show that transient transfection of T cells with CAR or sBite mRNA by electroporation can be an effective treatment platform as a cancer therapeutic.