Bispecific antibodies: a mechanistic review of the pipeline

Nat Rev Drug Discov. 2019 Aug;18(8):585-608. 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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Bispecific* / chemistry
  • Antibodies, Bispecific* / immunology
  • Antibodies, Bispecific* / therapeutic use
  • Binding Sites, Antibody
  • Clinical Trials as Topic
  • Drug Design*
  • Drug Evaluation, Preclinical
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms* / drug therapy
  • Neoplasms* / immunology


  • Antibodies, Bispecific