Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho- Maklaya St., 16/10, Moscow 117997, Russian Federation.
Real Target LLC, Miklukho-Maklaya st, 16/10, Moscow 117997, Russian Federation.
Curr Med Chem. 2019;26(3):396-426. doi: 10.2174/0929867324666170817152554.
Monoclonal antibodies (mAbs) are an important class of therapeutic agents approved for the therapy of many types of malignancies. However, in certain cases applications of conventional mAbs have several limitations in anticancer immunotherapy. These limitations include insufficient efficacy and adverse effects. The antigen-binding fragments of antibodies have a considerable potential to overcome the disadvantages of conventional mAbs, such as poor penetration into solid tumors and Fc-mediated bystander activation of the immune system. Fragments of antibodies retain antigen specificity and part of functional properties of conventional mAbs and at the same time have much better penetration into the tumors and a greatly reduced level of adverse effects. Recent advantages in antibody engineering allowed to produce different types of antibody fragments with improved structure and properties for efficient elimination of tumor cells. These molecules opened up new perspectives for anticancer therapy. Here, we will overview the structural features of the various types of antibody fragments and their applications for anticancer therapy as separate molecules and as part of complex conjugates or structures. Mechanisms of antitumor action of antibody fragments as well as their advantages and disadvantages for clinical application will be discussed in this review.
单克隆抗体（mAbs）是一类重要的治疗药物，已被批准用于治疗多种类型的恶性肿瘤。然而，在某些情况下，传统 mAbs 在癌症免疫治疗中的应用存在一些局限性。这些局限性包括疗效不足和不良反应。抗体的抗原结合片段具有克服传统 mAbs 缺点的巨大潜力，例如缺乏对实体瘤的穿透性和 Fc 介导的免疫系统旁观者激活。抗体片段保留了抗原特异性和传统 mAbs 的部分功能特性，同时具有更好的肿瘤穿透性和大大降低的不良反应水平。最近在抗体工程方面的优势使得能够生产出具有改进结构和性质的不同类型的抗体片段，以有效消除肿瘤细胞。这些分子为癌症治疗开辟了新的前景。在这里，我们将概述各种类型的抗体片段的结构特征及其作为单独分子以及作为复杂缀合物或结构的一部分用于癌症治疗的应用。本文将讨论抗体片段的抗肿瘤作用机制及其在临床应用中的优缺点。
