title: Inhibiting complement regulators in cancer immunotherapy with bispecific mAbs.
abstract: Although monoclonal antibody (mAb)-mediated immunotherapy of cancer has been proven to be feasible for clinical use, success rates until now have been disappointing. One reason for this might be the overexpression of membrane-bound complement regulatory proteins (mCRPs) by tumour cells. As complement activation is an important effector mechanism induced by therapeutic mAbs, inhibition of complement activation by tumour cells might reduce therapeutic efficacy by decreasing direct complement-mediated lysis as well as complement-dependent cellular cytotoxicity. Modulation of the function of these mCRPs might be achieved with therapeutic bispecific (bi-)mAbs that target a tumour antigen and simultaneously block a major mCRP. Clinical results will probably increase with such bi-mAbs compared with monovalent antitumour mAbs. In this review the feasibility of this approach is discussed.
authors.affiliation: Department of Medical Inflammation Research, Lund University, BMC I-11, 221 84 Lund, Sweden. Kyra.Gelderman@med.lu.se
authors.forename: Kyra A
authors.initials: KA
authors.lastname: Gelderman
authors.forename: Suzanne
authors.initials: S
authors.lastname: Lam
authors.forename: Arko
authors.initials: A
authors.lastname: Gorter
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D003169:Complement Inactivator Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*
chemical_list: D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D003169:Complement Inactivator Proteins