Bispecific antibodies: a mechanistic review of the pipeline

• Published in: Nature reviews. Drug discovery Vol. 18; no. 8; pp. 585 - 608
• Main Authors: Labrijn, Aran F, Janmaat, Maarten L, Reichert, Janice M, Parren, Paul W H I
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.08.2019
• Subjects: Animals; Antibodies; Antibodies, Bispecific - chemistry; Antibodies, Bispecific - immunology; Antibodies, Bispecific - therapeutic use; Antigens; Binding Sites, Antibody; Clinical Trials as Topic; Drug Design; Drug Evaluation, Preclinical; Drug targeting; Health aspects; Humans; Identification and classification; Molecular Targeted Therapy; Neoplasms - drug therapy; Neoplasms - immunology; Pharmaceutical research; Pipelines; Viral antibodies; Netherlands
• ISSN: 1474-1776; 1474-1784
• DOI: 10.1038/s41573-019-0028-1

The term bispecific antibody (bsAb) is used to describe a large family of molecules designed to recognize two different epitopes or antigens. BsAbs come in many formats, ranging from relatively small proteins, merely consisting of two linked antigen-binding fragments, to large immunoglobulin G (IgG)-like molecules with additional domains attached. An attractive bsAb feature is their potential for novel functionalities - that is, activities that do not exist in mixtures of the parental or reference antibodies. In these so-called obligate bsAbs, the physical linkage of the two binding specificities creates a dependency that can be temporal, with binding events occurring sequentially, or spatial, with binding events occurring simultaneously, such as in linking an effector to a target cell. To date, more than 20 different commercialized technology platforms are available for bsAb creation and development, 2 bsAbs are marketed and over 85 are in clinical development. Here, we review the current bsAb landscape from a mechanistic perspective, including a comprehensive overview of the pipeline.