Herceptin Research - Side-effects, Breast Cancer, Treatment, Therapy

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Active induction of tumor-specific IgE antibodies by oral mimotope vaccination.

Riemer AB, Untersmayr E, Knittelfelder R, Duschl A, Pehamberger H, Zielinski CC, Scheiner O, Jensen-Jarolim E

Departments of Pathophysiology, Dermatology, and Internal Medicine I, Medical University of Vienna, Vienna, Austria.

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.

Published 5 April 2007 in Cancer Res, 67(7): 3406-11.
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Herceptin Books

World Health Organization: Tumours of the Breast and Female Genital Organs (Who/IARC Classification of Tumours) (Who/IARC Classification of Tumours)

World Health Organization: Tumours of the Breast and Female Genital Organs (Who/IARC Classification of Tumours) (Who/IARC Classification of Tumours)