title: An antitumor cellular vaccine based on a mini-membrane IgE.
abstract: The IgE-mediated immune system activation can be redirected to combat tumors. Mouse and human IgE have been shown to provide a potent adjuvant effect in antitumor vaccination, with a crucial role played by FcεRI. This effect results from T cell-mediated adaptive immune response. Modified vaccinia virus Ankara (MVA) has been used to infect IgE-loaded tumor cells. These results led to a shift toward a highly safe protocol employing membrane IgE (mIgE), thus eliminating any possible anaphylactogenicity caused by circulating IgE. Evidence that human mIgE and a truncated version lacking IgE Fabs (tmIgE) bind and activate FcεRI has been fundamental and forms the core of this report. Human tmIgE has been engineered into a recombinant MVA (rMVA-tmIgE), and the expression of tmIgE and its transport to the surface of rMVA-tmIgE-infected cells has been detected by Western blot and cytofluorimetry, respectively. FcεRI activation by tmIgE has been confirmed by the release of β-hexosaminidase in a cell-to-cell contact assay using human FcεRI-transfected RBL-SX38 cells. The rMVA-tmIgE antitumor vaccination strategy has been investigated in FcεRIα(-/-) human FcεRIα(+) mice, with results indicating a level of protection comparable to that obtained using soluble human IgE tumor cell loading. The rMVA-tmIgE vector represents a device that suits safe IgE-based antitumor vaccines, harboring the possibility to couple tmIgE with other gene insertions that might enhance the antitumor effect, thus bringing the field closer to the clinics.
authors: Department of Biology and Genetics, Università degli Studi di Milano, Milan, Italy.
authors: Elisa A
authors: EA
authors: Nigro
authors: Elisa
authors: E
authors: Soprana
authors: Anna T
authors: AT
authors: Brini
authors: Alessandro
authors: A
authors: Ambrosi
authors: Vijay A
authors: VA
authors: Yenagi
authors: David
authors: D
authors: Dombrowicz
authors: Antonio G
authors: AG
authors: Siccardi
authors: Luca
authors: L
authors: Vangelista
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D014611:Vaccination; D014616:Vaccinia virus
chemical_list: D019496:Cancer Vaccines; D011994:Recombinant Proteins; D007073:Immunoglobulin E