title: Active induction of tumor-specific IgE antibodies by oral mimotope vaccination.
abstract: A role of IgE antibodies in cancer surveillance has been implicated for a long time. Studies dealing with IgE antibodies directly targeted to tumor antigens have shown marked anticancer effects mediated by this antibody class. Thus, the basic function of IgE antibodies may be to control tumor growth. Thus far, cancer-specific IgE has only been applied passively. Consequently, the aim of this study was to establish an active vaccination protocol to induce tumor antigen-specific IgE antibodies, and to evaluate functional properties. We previously generated epitope mimics, so-called mimotopes, for the epitope recognized by the anti-HER-2 antibody trastuzumab. Upon i.p. immunizations, IgG antibodies with trastuzumab-like properties could be elicited. In the present study, we immunized BALB/c mice via the oral route with these trastuzumab mimotopes, under simultaneous neutralization and suppression of gastric acid. As shown in preceding experiments, this feeding regimen effectively induces Th2 immune responses. Oral immunizations with trastuzumab mimotopes under hypoacidic conditions indeed resulted in the formation of IgE antibodies towards the HER-2 antigen. Moreover, anti-HER-2 IgE-sensitized effector cells mediated SK-BR-3 target cell lysis in an antibody-dependent cytotoxicity assay. We conclude that directed and epitope-specific induction of IgE against tumor antigens is feasible with an oral mimotope vaccination regimen, and that these antibodies mediate anticancer effects.
authors.affiliation: Departments of Pathophysiology, Dermatology, and Internal Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: Angelika B
authors.initials: AB
authors.lastname: Riemer
authors.forename: Eva
authors.initials: E
authors.lastname: Untersmayr
authors.forename: Regina
authors.initials: R
authors.lastname: Knittelfelder
authors.forename: Albert
authors.initials: A
authors.lastname: Duschl
authors.forename: Hubert
authors.initials: H
authors.lastname: Pehamberger
authors.forename: Christoph C
authors.initials: CC
authors.lastname: Zielinski
authors.forename: Otto
authors.initials: O
authors.lastname: Scheiner
authors.forename: Erika
authors.initials: E
authors.lastname: Jensen-Jarolim
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000096:biosynthesis* / Q000276:immunology; D000918:Antibody Specificity; D001943:Breast Neoplasms / Q000276:immunology* / Q000628:therapy*; D019496:Cancer Vaccines / Q000276:immunology* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000276:immunology; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; D007073:Immunoglobulin E; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab