Alternative molecular formats and therapeutic applications for bispecific antibodies

Mol Immunol. 2015 Oct;67(2 Pt A):95-106. doi: 10.1016/j.molimm.2015.01.003. Epub 2015 Jan 27.


Bispecific antibodies are on the cusp of coming of age as therapeutics more than half a century after they were first described. Two bispecific antibodies, catumaxomab (Removab(®), anti-EpCAM×anti-CD3) and blinatumomab (Blincyto(®), anti-CD19×anti-CD3) are approved for therapy, and >30 additional bispecific antibodies are currently in clinical development. Many of these investigational bispecific antibody drugs are designed to retarget T cells to kill tumor cells, whereas most others are intended to interact with two different disease mediators such as cell surface receptors, soluble ligands and other proteins. The modular architecture of antibodies has been exploited to create more than 60 different bispecific antibody formats. These formats vary in many ways including their molecular weight, number of antigen-binding sites, spatial relationship between different binding sites, valency for each antigen, ability to support secondary immune functions and pharmacokinetic half-life. These diverse formats provide great opportunity to tailor the design of bispecific antibodies to match the proposed mechanisms of action and the intended clinical application.

Keywords: Antibody engineering; Antibody therapeutics; Bispecific antibodies.

Publication types

  • Review

MeSH terms

  • Antibodies, Bispecific / immunology
  • Antibodies, Bispecific / metabolism
  • Antibodies, Bispecific / therapeutic use*
  • Antigens, CD19 / immunology
  • Antigens, CD19 / metabolism
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism
  • Antineoplastic Agents / immunology
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use
  • CD3 Complex / immunology
  • CD3 Complex / metabolism
  • Cell Adhesion Molecules / immunology
  • Cell Adhesion Molecules / metabolism
  • Epithelial Cell Adhesion Molecule
  • Humans
  • Immunotherapy / methods*
  • Models, Immunological
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / therapy*


  • Antibodies, Bispecific
  • Antigens, CD19
  • Antigens, Neoplasm
  • Antineoplastic Agents
  • CD3 Complex
  • Cell Adhesion Molecules
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule
  • blinatumomab
  • catumaxomab