title: Cutting edge: FcγRIII (CD16) and FcγRI (CD64) are responsible for anti-glycoprotein 75 monoclonal antibody TA99 therapy for experimental metastatic B16 melanoma.
abstract: mAb therapy for experimental metastatic melanoma relies on activating receptors for the Fc portion of IgG (FcγR). Opposing results on the respective contribution of mouse FcγRI, FcγRIII, and FcγRIV have been reported using the gp75-expressing B16 melanoma and the protective anti-gp75 mAb TA99. We analyzed the contribution of FcγRs to this therapy model using bioluminescent measurement of lung metastases loads, novel mouse strains, and anti-FcγR blocking mAbs. We found that the TA99 mAb-mediated effects in a combination therapy using cyclophosphamide relied on activating FcγRs. The combination therapy, however, was not more efficient than mAb therapy alone. We demonstrate that FcγRI and, unexpectedly, FcγRIII contributed to TA99 mAb therapeutic effects, whereas FcγRIV did not. Therefore, FcγRIII and FcγRI are, together, responsible for anti-gp75 mAb therapy of B16 lung metastases. Our finding that mouse FcγRIII contributes to Ab-induced tumor reduction correlates with clinical data on its human functional equivalent human FcγRIIIA (CD16A).
authors.affiliation: Institut Pasteur, [corrected] Département d'Immunologie, Unité d'Allergologie Moléculaire et Cellulaire, [corrected] 75015 Paris, France.
authors.forename: Marcello
authors.initials: M
authors.lastname: Albanesi
authors.forename: David A
authors.initials: DA
authors.lastname: Mancardi
authors.forename: Lynn E
authors.initials: LE
authors.lastname: Macdonald
authors.forename: Bruno
authors.initials: B
authors.lastname: Iannascoli
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murphy
authors.forename: Marc
authors.initials: M
authors.lastname: Daëron
authors.forename: Jeanette H
authors.initials: JH
authors.lastname: Leusen
authors.forename: Pierre
authors.initials: P
authors.lastname: Bruhns
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001103:Arboviruses / Q000276:immunology; D006825:Hybridomas; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000627:therapeutic use*; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; C485701:Fcgr1 protein, mouse; C485700:Fcgr3 protein, mouse; D017452:Receptors, IgG; D014764:Viral Proteins; C072449:glycoprotein 75, Thogoto virus