Effector-cell-engaging bispecific antibodies for cancer therapeutics: engineering precision immunity.

Abstract

The bispecific antibody (bsAb) is a novel immune therapeutic platform that consists of a single molecule that simultaneously binds two distinct antigens, tumor-associated antigens and immune effector cells, to enhance the targeted killing of tumor cells. bsAbs can target T cells and natural killer (NK) cells or macrophages through receptors such as CD3, CD16 or CD47 and generate strong, MHC-independent antitumor activity. This review outlines the evolution of effector-cell-engaging bsAb formats, such as BiTEs, DARTs, TandAbs and IgG-like constructs, along with engineering strategies to enhance Fc function, valency, half-life, safety and efficacy. It describes clinically validated T-cell engagers, new NK-cell- and macrophage-targeting bsAbs, trispecific NK engagers, tumor-activated and mRNA-encoded bsAbs, and combination strategies with checkpoint inhibitors and cellular therapies, highlighting their role in precision oncology.