Development of antibody-like T-cell engager based on VH-VL heterodimer formation and its application in cancer therapy

Abstract

Last decade, various bispecific antibody formats using T-cells to kill tumor cells have been developed in order to obtain improved effects clinically beyond the low response rate of conventional monoclonal antibody therapy. T- cell bispecific antibody (T-cell engager) targets specific antigens on surface of cancer cells and eliminates cancer cells by making immunological synapse and activating effector T-cells. Although T-cell engager shows superior anti-cancer effects in the clinic compared to conventional monoclonal antibody, there are hurdles such as physicochemical properties, productivity, and toxicity (CRS) to engineer/develop bispecific antibody. This dissertation discusses the development of a novel T-cell bispecific antibody platform (Antibody Like (T) Cell Engager, ALiCE) using an antibody assembly mechanism. In addition, it introduces the research results of ALiCE molecule engineered with anti-PD-L1 mAb and anti-CD3 mAb, and in-depth analysis on the advantages and specificities of ALiCE.