Neutrophil Fc gamma RI as target for immunotherapy of invasive candidiasis.
Invasive candidiasis represents a life-threatening disease for immunocompromised patients. This study focused on new immunotherapeutic approaches for systemic Candida albicans infections in a human FcgammaRI-transgenic mouse model. FcgammaRI (CD64) is a potent immunoactivating receptor on phagocytic and dendritic cells. In vivo targeting of C. albicans toward neutrophil-FcgammaRI by bispecific Abs and G-CSF effectively protected FcgammaRI-transgenic mice from lethal candidiasis. Nontransgenic mice were not protected, and treatment with bispecific Ab or G-CSF alone did not reduce mortality. Furthermore, infected FcgammaRI-transgenic mice developed high titers of anti-C. albicans IgG, and survival was extended on secondary infection without further treatment. These findings document the capacity of FcgammaRI to initiate potent anti-C. albicans immunity and support the development of FcgammaRI-directed immunotherapy of invasive fungal disease.
van Spriel
A B
AB
Immunotherapy Laboratory, Medarex Europe, and Genmab, University Medical Center, Utrecht, The Netherlands.
van den Herik-Oudijk
I E
IE
van de Winkel
J G
JG
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000235:genetics; D000818:Animals; D018033:Antibodies, Bispecific / Q000008:administration & dosage; D002177:Candidiasis / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D004359:Drug Therapy, Combination; D005260:Female; D018390:Gene Targeting; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000235:genetics; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism*; D010587:Phagocytosis / Q000276:immunology; D011092:Polyethylene Glycols / Q000008:administration & dosage; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012008:Recurrence; D015996:Survival Rate
D000276:Adjuvants, Immunologic; D018033:Antibodies, Bispecific; D017452:Receptors, IgG; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D011092:Polyethylene Glycols