In vitro characterization of HER2-redirected universal CAR T cells

Abstract

The thesis provides a comprehensive study on the development and application of Universal CAR T cells (UniCAR T cells) targeted against the HER2 antigen, which is commonly overexpressed in various cancers. The introduction efficiently outlines the context of conventional CAR T cell therapies and their limitations, which sets the stage for the innovative approach of using UniCAR T cells that can be universally applied across different antigens via a modular approach. In this study, UniCAR encoding retro- and lentiviral vectors were produced by replacing the HER2-recognition domain with the mSA2 biotin-binding domain, leading to UniCAR expression in 10-13% of human PBMCs. Coculture assays revealed that biotin-trastuzumab induced HER2-specific UniCAR T cell activation, resulting in IFNγ secretion and targeted lysis of MDA-HER2 tumor cells. Retroviral UniCAR exhibited superior T cell activation in ELISA assays. Novel findings in this topic could revolutionize cancer treatment by offering a highly targeted therapy that reduces off-target effects, potentially leading to improved outcomes and pave the way for innovative approaches in autoimmune disease management.