title: When binding is enough: nonactivating antibody formats.
abstract: 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.
authors.affiliation: Genmab, Yalelaan 60, Utrecht, The Netherlands. a.labrijn@genmab.com
authors.forename: Aran F
authors.initials: AF
authors.lastname: Labrijn
authors.forename: Rob C
authors.initials: RC
authors.lastname: Aalberse
authors.forename: Janine
authors.initials: J
authors.lastname: Schuurman
mesh_terms: D019138:Antibodies, Blocking / Q000276:immunology* / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use; D007132:Immunoglobulin Isotypes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use; D015202:Protein Engineering
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes