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首页> 外文期刊>Journal of Hematology and Oncology >How to select IgG subclasses in developing anti-tumor therapeutic antibodies
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How to select IgG subclasses in developing anti-tumor therapeutic antibodies

机译：如何选择抗肿瘤治疗抗体的IgG亚类

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The intact antibody of human immunoglobulin (IgG) is composed of the fragment for antigen binding (Fab) and the crystallizable fragment (Fc) for binding of Fcγ receptors. Among the four subclasses of human IgG (IgG1, IgG2, IgG3, IgG4), which differ in their constant regions, particularly in their hinges and CH2 domains, IgG1 has the highest FcγR-binding affinity, followed by IgG3, IgG2, and IgG4. As a result, different subclasses have different effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Fcγ receptors include six subtypes (FcγRI, FcγRIIA, FcγRIIB, FcγRIIC, FcγRIIIA, FcγRIIIB) which differ in cellular distribution, binding affinity to Fc, and the resulting biological activity. Therefore, when developing anti-tumor therapeutic antibodies, including single-targeted antibodies, bi-specific antibodies (BsAbs), and antibody-drug conjugates (ADCs), many factors, such as target biology, cellular distribution of the targets, the environments of particular tumor types, as well as the proposed mechanism of action (MOA), must be taken into consideration. This review outlines fundamental strategies that are required to select IgG subclasses in developing anti-tumor therapeutic antibodies.
机译：人免疫球蛋白（IgG）的完整抗体由用于抗原结合（Fab）的片段和用于结合Fcγ受体的结晶片段（Fc）组成。在人IgG（IgG1，IgG2，IgG3，IgG3）的四个亚类中，其在其恒定区域中不同，特别是在其铰链和CH2结构域中，IgG1具有最高的FcγR结合亲和力，其次是IgG3，IgG2和IgG4。结果，不同的亚类具有不同的效应器功能，例如抗体依赖性细胞介导的细胞毒性（ADCC）和抗体依赖性细胞吞噬作用（ADCP）。 Fcγ受体包括六个亚型（FcγRI，FcγRIIA，FcγRIIB，Fcγ，Fcγ，FcγRIIIB，FCγRIIIB），其不同于细胞分布，对Fc的亲和力结合，以及所得的生物活性。因此，当开发抗肿瘤治疗抗体，包括单靶向抗体，双特异性抗体（BSAB）和抗体 - 药物缀合物（ADC），许多因素，例如靶生物学，靶标的细胞分布，环境必须考虑特定的肿瘤类型，以及所提出的行动机制（MOA）。本次审查概述了在开发抗肿瘤治疗抗体方面选择IgG亚类所需的基本策略。

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