Jefferis Roy
University of Birmingham, Division of Immunity & Infection, The School of Medicine, Edgbaston, Birmingham B15 2TT, UK.
Expert Opin Biol Ther. 2007 Sep;7(9):1401-13. doi: 10.1517/14712598.7.9.1401.
Recombinant monoclonal antibody (rMAb) therapy may be instituted to achieve one of two broad outcomes: i) killing of cells or organisms (e.g., cancer cells, bacteria); and ii) neutralisation of soluble molecules (e.g., cytokines in chronic disease or toxins in infection). The choice of rMAb isotype is a critical decision in the development of a therapeutic antibody as it will determine the biological activities triggered in vivo. It is not possible, however, to accurately predict the in vivo activity because multiple parameters impact on the functional outcome, for example, IgG subclass, IgG-Fc glycoform, epitope density, cellular Fc receptors polymorphisms and so on. The present understanding of the molecular interactions between IgG-Fc and effector ligands in vitro has allowed the generation of new antibody structures with altered/improved effector function profiles that may prove optimal for given disease indications. Thus, when maximal antibody-dependent cell-mediated cytotoxicity activity is indicated a non-fucosylated IgG1 format may be optimal; when minimal activity is indicated an aglycosylated IgG2 may be the form of choice.
重组单克隆抗体（rMAb）疗法可用于实现两个主要结果之一：i）杀死细胞或生物体（如癌细胞、细菌）；ii）中和可溶性分子（如慢性病中的细胞因子或感染中的毒素）。在治疗性抗体的研发中，选择rMAb的亚型是一个关键决策，因为它将决定体内引发的生物学活性。然而，由于多种参数会影响功能结果，例如IgG亚类、IgG-Fc糖型、表位密度、细胞Fc受体多态性等，所以无法准确预测体内活性。目前对IgG-Fc与效应配体在体外分子相互作用的理解，使得能够产生具有改变/改善效应功能谱的新抗体结构，这些结构可能被证明对特定疾病适应症是最佳的。因此，当需要最大程度的抗体依赖性细胞介导的细胞毒性活性时，非岩藻糖基化的IgG1形式可能是最佳的；当需要最小活性时，无糖基化的IgG2可能是首选形式。
