The high-affinity IgG receptor, FcgammaRI, plays a central role in antibody therapy of experimental melanoma.
We examined the role of FcgammaR in antibody therapy of metastatic melanoma in wild-type and different FcgammaR knock-out mice. Treatment of B16F10-challenged wild-type mice with TA99 antibody specific for the gp75 tumor antigen resulted in a marked decrease in numbers of lung metastases. Treatment of individual FcgammaR knock-out mice revealed the high-affinity IgG receptor, FcgammaRI (CD64), to represent the central FcgammaR for TA99-induced antitumor effects. The potential of immune-modulating agents to further enhance the protective effect induced by monoclonal antibody (mAb) TA99 was examined in combination treatments consisting of mAb TA99 and a TLR-4 agonist, monophosphoryl lipid A (MPL). MPL did potently boost TA99 antibody-induced effects, and combination therapy was, again, found to be dependent on the presence of FcgammaRI.
Bevaart
Lisette
L
Immunotherapy Laboratory, Department of Immunology, University Medical Center Utrecht, Lundlaan 6, 3584 EA Utrecht, the Netherlands.
Jansen
Marco J H
MJ
van Vugt
Martine J
MJ
Verbeek
J Sjef
JS
van de Winkel
Jan G J
JG
Leusen
Jeanette H W
JH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology*; D000918:Antibody Specificity; D007116:Immunization, Passive / Q000379:methods; D008050:Lipid A / Q000031:analogs & derivatives / Q000276:immunology / Q000494:pharmacology; D008175:Lung Neoplasms / Q000556:secondary; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; C485701:Fcgr1 protein, mouse; D008050:Lipid A; D017452:Receptors, IgG; C048436:monophosphoryl lipid A