Sep 2026· Drug Discovery Today· pp.
104800
· 0 citations· 125 references
Medicine
TL;DR
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.
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.
Bispecific antibodies (BsAbs) are emerging immunotherapeutics that simultaneously engage two distinct targets. This property provides unique mechanisms of action that are not achieved by conventional monoclonal antibodies, including cell-cell bridging, modulation of multiple signaling pathways, and recruitment of diver...
Toshiya Hino, Yusuke Ito, Yuki Kagoya· International Immunology· 0 citations
This review consolidates recent developments in CD3-engaging bispecific antibody engineering, including format optimization, affinity modulation, selectivity enhancement, and half-life prolongation, as well as clinical applications in hematologic and solid malignancies.
Ali Najafyar, Z. Hajihassan, W. Ibrahim· Discover Oncology· 0 citations
BSAbs and bsADCs provide opportunities to improve tumor selectivity, enhance internalization, overcome antigen escape, and expand the population of CRC patients eligible for targeted therapy, as well as discussing the major challenges facing clinical translation.
Maya G. Cappellino, Sean P. Sullivan, Peyton C. High et al.· Antibodies· 0 citations
Bispecific antibodies have gradually been applied in the treatment of multiple myeloma(MM). The combination of bispecific antibodies targeting CD3 and CD28 mimics the dual-signaling system (antigen signaling and co-stimulatory signaling) of natural T cell activation, thereby significantly enhancing the anti-tumor res...
Chaofan Wang, Wanting Wang, Mo-Ran Wang et al.· Cell Death & Disease· 0 citations
Monoclonal antibodies (mAbs) are a cornerstone of cancer therapy. They offer high target specificity and diverse cytotoxic mechanisms, which render them superior to many conventional cytotoxic treatments. This review examines therapeutic mAbs from two aspects. First, their mechanisms of action are analysed, including d...
Ye-Mei Chen· Theoretical and Natural Scie...· 0 citations
Chimeric antigen receptor (CAR)-based cell therapies have transformed the treatment of selected hematologic malignancies, yet their efficacy in solid tumors remains limited due to antigen heterogeneity, inadequate trafficking, physical and metabolic barriers, immune suppression, and poor persistence of transferred cell...
