Antitumor IgE adjuvanticity: key role of Fc epsilon RI.
Working with C57BL/6 mouse tumor models, we had previously demonstrated that vaccination with IgE-coated tumor cells can protect against tumor challenge, an observation that supports the involvement of IgE in antitumor immunity. The adjuvant effect of IgE was shown to result from eosinophil-dependent priming of the T cell-mediated adaptive immune response. The protective effect is likely to be mediated by the interaction of tumor cell-bound IgE with receptors, which then trigger the release of mediators, recruitment of effector cells, cell killing and tumor Ag cross-priming. It was therefore of utmost importance to demonstrate the strict dependence of the protective effect on IgE receptor activation. First, the protective effect of IgE was confirmed in a BALB/c tumor model, in which IgE-loaded modified VV Ankara-infected tumor cells proved to be an effective cellular vaccine. However, the protective effect was lost in Fc(epsilon)RIalpha(-/-) (but not in CD23(-/-)) knockout mice, showing the IgE-Fc(epsilo)nRI interaction to be essential. Moreover, human IgE (not effective in BALB/c mice) had a protective effect in the humanized knockin mouse (Fc(epsilon)RIalpha(-/-) hFc(epsilon)RIalpha(+)). This finding suggests that the adjuvant effect of IgE could be exploited for human therapeutics.
Nigro
Elisa A
EA
Department of Biology and Genetics, University of Milan, Milan, Italy.
Brini
Anna T
AT
Soprana
Elisa
E
Ambrosi
Alessandro
A
Dombrowicz
David
D
Siccardi
Antonio G
AG
Vangelista
Luca
L
D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use*; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D055879:Gene Knock-In Techniques; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use*; D015471:Leukemia, Basophilic, Acute / Q000276:immunology / Q000473:pathology / Q000628:therapy; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051381:Rats; D017455:Receptors, IgE / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D003432:Cross-Linking Reagents; D017455:Receptors, IgE; D007073:Immunoglobulin E