Derer Stefanie, Kellner Christian, Rösner Thies, Klausz Katja, Glorius Pia, Valerius Thomas, Peipp Matthias
Division for Stem Cell Transplantation and Immunotherapy, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Kiel, Germany.
Methods Mol Biol. 2014;1131:525-40. doi: 10.1007/978-1-62703-992-5_33.
Therapeutic antibodies used in the treatment of cancer patients are able to mediate diverse effector mechanisms. Dependent on tumor entity, localization, and tumor burden different effector mechanisms may contribute to the in vivo antitumor activity to a variable degree. Especially Fc-mediated effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) have been suggested as being important for the in vivo activity of therapeutic antibodies like rituximab or trastuzumab. In recent years, several strategies have been pursued to further optimize the cytotoxic potential of monoclonal antibodies by modifying their Fc part (Fc engineering) with the ultimate goal to enhance antibody therapy.Since Fc engineering approaches are applicable to any Fc-containing molecule, strategies to enhance CDC or ADCC activity of full antibodies or scFv-Fc fusion proteins by altering the primary Fc sequence are described.
用于治疗癌症患者的治疗性抗体能够介导多种效应机制。根据肿瘤实体、定位和肿瘤负荷的不同，不同的效应机制可能在不同程度上对体内抗肿瘤活性有所贡献。特别是Fc介导的效应功能，如抗体依赖性细胞介导的细胞毒性（ADCC）和补体依赖性细胞毒性（CDC），已被认为对于利妥昔单抗或曲妥珠单抗等治疗性抗体的体内活性很重要。近年来，人们采用了几种策略，通过修饰其Fc部分（Fc工程）来进一步优化单克隆抗体的细胞毒性潜力，最终目标是增强抗体治疗效果。由于Fc工程方法适用于任何含Fc的分子，因此本文描述了通过改变主要Fc序列来增强完整抗体或scFv-Fc融合蛋白的CDC或ADCC活性的策略。
