Riemer Angelika B, Untersmayr Eva, Knittelfelder Regina, Duschl Albert, Pehamberger Hubert, Zielinski Christoph C, Scheiner Otto, Jensen-Jarolim Erika
Departments of Pathophysiology, Dermatology, and Internal Medicine I, Medical University of Vienna, Vienna, Austria.
Cancer Res. 2007 Apr 1;67(7):3406-11. doi: 10.1158/0008-5472.CAN-06-3758.
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.
长期以来，人们一直认为IgE抗体在癌症监测中发挥作用。针对直接靶向肿瘤抗原的IgE抗体的研究表明，这类抗体具有显著的抗癌作用。因此，IgE抗体的基本功能可能是控制肿瘤生长。到目前为止，癌症特异性IgE仅被被动应用。因此，本研究的目的是建立一种主动疫苗接种方案，以诱导肿瘤抗原特异性IgE抗体，并评估其功能特性。我们之前为抗HER-2抗体曲妥珠单抗识别的表位生成了表位模拟物，即所谓的模拟表位。经腹腔免疫后，可引发具有曲妥珠单抗样特性的IgG抗体。在本研究中，我们在中和并抑制胃酸的同时，通过口服途径用这些曲妥珠单抗模拟表位免疫BALB/c小鼠。如先前实验所示，这种喂养方案可有效诱导Th2免疫反应。在胃酸过少的条件下，用曲妥珠单抗模拟表位进行口服免疫确实导致了针对HER-2抗原的IgE抗体的形成。此外，在抗体依赖性细胞毒性试验中，抗HER-2 IgE致敏的效应细胞介导了SK-BR-3靶细胞的裂解。我们得出结论，通过口服模拟表位疫苗接种方案定向和表位特异性诱导针对肿瘤抗原的IgE是可行的，并且这些抗体介导抗癌作用。
