title: IgEs targeted on tumor cells: therapeutic activity and potential in the design of tumor vaccines.
abstract: Surface-bound IgE play a central role in antiparasite immunity; to exploit IgE-driven immune mechanisms in tumor prevention and control, monoclonal IgEs of irrelevant specificity were loaded through biotin-avidin bridging onto tumor cells, either by systemic administration to tumor-bearing mice or pre-loading of tumor cells before inoculation. Here we show that systemic administration of biotinylated IgEs to mice bearing tumors pre-targeted with biotinylated antibodies and avidin significantly decreased tumor growth rate. In addition, as compared with IgG-loaded control cells, inoculation of suboptimal doses of IgE-loaded tumor cells suppressed tumor formation in a fraction of animals and induced protective host immunity by eliciting tumor-specific T-cell responses. Similarly, tumor vaccination experiments showed that irradiated tumor cells (IgE loaded by biotin-avidin bridging) conferred protective immunity at doses 100-fold lower than the corresponding control cells without IgE. Finally, in vivo depletion of eosinophils or T cells abrogated IgE-driven tumor growth inhibition. These results demonstrate that IgEs targeted on tumor cells not only possess a curative potential but also confer long-term antitumor immunity and that IgE-driven antitumor activity is not restricted to the activation of innate immunity effector mechanisms but also results from eosinophil-dependent priming of a T-cell-mediated adaptive immune response. This suggests a potential role for IgEs in the design of new cell-based tumor vaccines.
authors.affiliation: San Raffaele Scientific Institute, Milan, Italy. realie@mail.nih.gov
authors.forename: E
authors.initials: E
authors.lastname: Reali
authors.forename: J W
authors.initials: JW
authors.lastname: Greiner
authors.forename: A
authors.initials: A
authors.lastname: Corti
authors.forename: H J
authors.initials: HJ
authors.lastname: Gould
authors.forename: F
authors.initials: F
authors.lastname: Bottazzoli
authors.forename: G
authors.initials: G
authors.lastname: Paganelli
authors.forename: J
authors.initials: J
authors.lastname: Schlom
authors.forename: A G
authors.initials: AG
authors.lastname: Siccardi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology*; D015848:Interleukin-5 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000528:radiation effects
chemical_list: D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D015848:Interleukin-5; D007073:Immunoglobulin E