Jensen-Jarolim E, Achatz G, Turner M C, Karagiannis S, Legrand F, Capron M, Penichet M L, Rodríguez J A, Siccardi A G, Vangelista L, Riemer A B, Gould H
Department of Pathophysiology, Center of Physiology, Pathophysiology and Immunology, Medical University Vienna, Austria.
Allergy. 2008 Oct;63(10):1255-66. doi: 10.1111/j.1398-9995.2008.01768.x. Epub 2008 Jul 26.
Epidemiological studies have suggested inverse associations between allergic diseases and malignancies. As a proof of concept for the capability of immunoglobulin E (IgE) to destruct tumor cells, several experimental strategies have evolved to specifically target this antibody class towards relevant tumor antigens. It could be demonstrated that IgE antibodies specific to overexpressed tumor antigens have been superior to any other immunoglobulin class with respect to antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) reactions. In an alternative approach, IgE nonspecifically attached to tumor cells proved to be a powerful adjuvant establishing tumor-specific immune memory. Active Th2 immunity could also be achieved by applying an oral immunization regimen using mimotopes, i.e. epitope mimics of tumor antigens. The induced IgE antibodies could be cross-linked by live tumor cells leading to tumoricidic mediator release. Thus, IgE antibodies may not only act in natural tumor surveillance, but could possibly also be exploited for tumor control in active and passive immunotherapy settings. Thereby, eosinophils, mast cells and macrophages can be armed with the cytophilic IgE and become potent anti-tumor effectors, able to trace viable tumor cells in the tissues. It is strongly suggested that the evolving new field AllergoOncology will give new insights into the role of IgE-mediated allergy in malignancies, possibly opening new avenues for tumor therapy.
流行病学研究表明,过敏性疾病与恶性肿瘤之间存在负相关关系。作为免疫球蛋白E(IgE)破坏肿瘤细胞能力的概念验证,已开发出几种实验策略,以将这种抗体特异性靶向相关肿瘤抗原。可以证明,针对过表达肿瘤抗原的IgE抗体在抗体依赖性细胞毒性(ADCC)和吞噬作用(ADCP)反应方面优于任何其他免疫球蛋白类别。在另一种方法中,非特异性附着于肿瘤细胞的IgE被证明是建立肿瘤特异性免疫记忆的有力佐剂。通过使用模拟表位(即肿瘤抗原的表位模拟物)进行口服免疫方案,也可以实现活跃的Th2免疫。诱导产生的IgE抗体可被活肿瘤细胞交联,导致杀肿瘤介质释放。因此,IgE抗体不仅可能在天然肿瘤监测中发挥作用,而且在主动和被动免疫治疗环境中也可能被用于肿瘤控制。由此,嗜酸性粒细胞、肥大细胞和巨噬细胞可携带亲细胞性IgE并成为有效的抗肿瘤效应细胞,能够在组织中追踪存活的肿瘤细胞。强烈建议,新兴的过敏肿瘤学领域将为IgE介导的过敏在恶性肿瘤中的作用提供新的见解,可能为肿瘤治疗开辟新途径。