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 Ig Es of irrelevant specificity were loaded through biotin-avidin bridging ont o tumor cells, either by systemic administration to tumor-bearing mice or p re-loading of tumor cells before inoculation. Here we show that systemic ad ministration of biotinylated IgEs to mice bearing tumors pre-targeted with biotinylated antibodies and avidin significantly decreased tumor growth rat e. In addition, as compared with IgC-loaded control cells, inoculation of s uboptimal doses of IgE-loaded tumor cells suppressed tumor formation in a f raction 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) conferre d protective immunity at doses 100-fold lower than the corresponding contro l cells without IgE, Finally, in vivo depletion of eosinophils or T cells a brogated IgE-driven tumor growth inhibition. These results demonstrate that IgEs targeted on tumor cells not only possess a curative potential but als o confer long-term antitumor immunity and that IgE-driven antitumor activit y is not restricted to the activation of innate immunity effector mechanism s but also results from eosinophil-dependent priming of a T-cell-mediated a daptive immune response. This suggests a potential role for IgEs in the des ign of new cell-based tumor vaccines.