When binding is enough: nonactivating antibody formats

Curr Opin Immunol. 2008 Aug;20(4):479-85. doi: 10.1016/j.coi.2008.05.010. Epub 2008 Jul 9.


Most therapeutic antibodies currently used in the clinic are based on the human IgG1 format, which is a bivalent molecule that efficiently interacts with the immune system's effector functions. In clinical applications where binding to the target alone is sufficient for therapeutic efficacy; however, engagement of the immune system is not required and may even cause unwanted side-effects. Likewise, bivalent binding to the target may negatively influence the therapeutic efficacy of an antibody. Here we discuss the state of the art for antibody-based therapeutics, designed to be nonactivating (i.e. do not engage the innate immune system's effector functions), in both monovalent and bivalent formats.

Publication types

  • Review

MeSH terms

  • Antibodies, Blocking / immunology*
  • Antibodies, Blocking / metabolism
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Monoclonal / therapeutic use
  • Humans
  • Immunoglobulin Fc Fragments / chemistry
  • Immunoglobulin Fc Fragments / immunology*
  • Immunoglobulin Fc Fragments / metabolism
  • Immunoglobulin Fc Fragments / therapeutic use
  • Immunoglobulin G / chemistry
  • Immunoglobulin G / genetics
  • Immunoglobulin G / immunology*
  • Immunoglobulin G / metabolism
  • Immunoglobulin G / therapeutic use
  • Immunoglobulin Isotypes / chemistry
  • Immunoglobulin Isotypes / immunology*
  • Immunoglobulin Isotypes / metabolism
  • Immunoglobulin Isotypes / therapeutic use
  • Protein Engineering


  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • Immunoglobulin Isotypes