IgEs targeted on tumor cells: therapeutic activity and potential in the design of tumor vaccines.
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.
Reali
E
E
San Raffaele Scientific Institute, Milan, Italy. realie@mail.nih.gov
Greiner
J W
JW
Corti
A
A
Gould
H J
HJ
Bottazzoli
F
F
Paganelli
G
G
Schlom
J
J
Siccardi
A G
AG
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
D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D015848:Interleukin-5; D007073:Immunoglobulin E