Derer Stefanie, Kellner Christian, Berger Sven, Valerius Thomas, Peipp Matthias
Division for Stem Cell Transplantation and Immunotherapy, Department of Medicine II, University Hospital Schleswig-Holstein and Christian-Albrechts-University, Kiel, Germany.
Methods Mol Biol. 2012;907:519-36. doi: 10.1007/978-1-61779-974-7_30.
Today monoclonal antibodies are widely used in cancer therapy. However, clinical experience as well as translational research into antibodies' pharmacology and effector mechanisms has identified limitations of antibody therapy, including inefficient effector cell recruitment or initiation of complement-dependent cytotoxicity (CDC). These insights opened alleys for further improvement of antibodies' immunomodulatory functions. While second generation antibodies were predominantly engineered to reduce immunogenicity, progress in antibody engineering now enables the generation of antibodies with novel interesting features. The introduction of Fc engineering technologies offers the potential to tailor Fc-mediated effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC), CDC or phagocytosis. Approaches to improve Fc-mediated effector mechanisms by Fc-engineering allow for the design of so-called "fit-for-purpose" antibodies or antibody-derivatives, hopefully overcoming some limitations of current forms of antibody therapy.
如今，单克隆抗体在癌症治疗中被广泛应用。然而，临床经验以及对抗体药理学和效应机制的转化研究已经明确了抗体疗法的局限性，包括效应细胞募集效率低下或补体依赖性细胞毒性（CDC）启动不足。这些见解为进一步改善抗体的免疫调节功能开辟了道路。虽然第二代抗体主要是为降低免疫原性而设计的，但如今抗体工程的进展使得能够产生具有新颖有趣特性的抗体。Fc工程技术的引入为定制Fc介导的效应功能提供了潜力，如抗体依赖性细胞介导的细胞毒性（ADCC）、CDC或吞噬作用。通过Fc工程改善Fc介导效应机制的方法有助于设计所谓的“适用型”抗体或抗体衍生物，有望克服当前抗体疗法形式的一些局限性。
