文章：

癌症的抗体治疗

Antibody therapy of cancer

原文发布日期：2012-03-22

DOI: 10.1038/nrc3236

类型: Review Article

开放获取: 否

要点：

1. Antibody-based therapy for cancer has become established over the past 15 years and is now one of the most successful and important strategies for treating patients with haematological malignancies and solid tumours.
2. Evidence from clinical trials of antibodies in cancer patients has revealed the importance of iterative approaches for the selection of antigen targets and optimal antibodies.
3. The killing of tumour cells using monoclonal antibodies (mAbs) can result from direct action of the antibody (through receptor blockade, for example), immune-mediated cell killing mechanisms, payload delivery, and specific effects of an antibody on the tumour vasculature and stroma.
4. Tumour antigens that have been successfully targeted include epidermal growth factor receptor (EGFR), ERBB2, vascular endothelial growth factor (VEGF), cytotoxic T lymphocyte-associated antigen 4 (CTLA4), CD20, CD30 and CD52.
5. Serological, genomic, proteomic and bioinformatic databases have also been used to identify antigens and receptors that are overexpressed in tumour cell populations or that are linked to gene mutations identified as driving cancer cell proliferation, including EGFRvIII, MET, CTLA4 and fibroblast activation protein (FAP).
6. The successful development of candidate mAbs for the clinic involves a complex process of scientific and preclinical evaluations that include identification of the physical and chemical properties of the antibody; the detailed specificity analysis of antigen expression; the study of the immune effector functions and signalling pathway effects of the antibody; the analysis of in vivo antibody localization and distribution in transplanted or syngeneic tumour systems; and the observation of the in vivo therapeutic activity of the antibody.
7. A major objective for the clinical evaluation of mAbs has been determining the toxicity and therapeutic efficacy of the antibody alone or as a delivery system for radioisotopes or other toxic agents. It is also crucial to assess its in vivo specificity by determining its biodistribution in patients and to assess the ratio of antibody uptake in the tumour versus normal tissues.
8. Twelve antibodies have received approval from the US Food and Drug Administration for the treatment of various solid tumours and haematological malignancies, and a large number of additional therapeutic antibodies are currently being tested in early stage and late-stage clinical trials.

要点翻译：

1. 基于抗体的癌症疗法在过去15年中已经确立，现已成为治疗血液系统恶性肿瘤和实体瘤患者最成功和重要的策略之一。
2. 来自癌症患者抗体临床试验的证据揭示了迭代方法在选择抗原靶点和优化抗体方面的重要性。
3. 使用单克隆抗体（mAbs）杀死肿瘤细胞可能源于抗体的直接作用（例如通过受体阻断）、免疫介导的细胞杀伤机制、有效载荷递送，以及抗体对肿瘤血管系统和基质的特定影响。
4. 已成功靶向的肿瘤抗原包括表皮生长因子受体（EGFR）、ERBB2、血管内皮生长因子（VEGF）、细胞毒性T淋巴细胞相关抗原4（CTLA4）、CD20、CD30和CD52。
5. 血清学、基因组学、蛋白质组学和生物信息学数据库也被用于识别在肿瘤细胞群体中过表达或与驱动癌细胞增殖的基因突变相关的抗原和受体，包括EGFRvIII、MET、CTLA4和成纤维细胞激活蛋白（FAP）。
6. 候选单克隆抗体成功进入临床涉及复杂的科学和临床前评估过程，包括鉴定抗体的物理和化学性质；对抗原表达的详细特异性分析；研究抗体的免疫效应功能和信号通路影响；分析抗体在移植或同系肿瘤系统中的体内定位和分布；以及观察抗体的体内治疗活性。
7. 单克隆抗体临床评估的一个主要目标是确定抗体单独使用或作为放射性同位素或其他毒性药物的递送系统时的毒性和治疗效果。通过确定其在患者体内的生物分布并评估抗体在肿瘤与正常组织中的摄取比率，来评估其体内特异性也至关重要。
8. 已有12种抗体获得美国食品药品监督管理局批准用于治疗各种实体瘤和血液系统恶性肿瘤，并且大量其他治疗性抗体目前正处于早期和晚期临床试验阶段。

英文摘要：

The use of monoclonal antibodies (mAbs) for cancer therapy has achieved considerable success in recent years. Antibody–drug conjugates are powerful new treatment options for lymphomas and solid tumours, and immunomodulatory antibodies have also recently achieved remarkable clinical success. The development of therapeutic antibodies requires a deep understanding of cancer serology, protein-engineering techniques, mechanisms of action and resistance, and the interplay between the immune system and cancer cells. This Review outlines the fundamental strategies that are required to develop antibody therapies for cancer patients through iterative approaches to target and antibody selection, extending from preclinical studies to human trials.

摘要翻译： 

近年来，单克隆抗体（mAbs）用于癌症治疗取得了显著成功。抗体-药物偶联物为淋巴瘤和实体瘤提供了强有力的全新治疗选择，免疫调节抗体亦在近期取得了卓越的临床成果。治疗性抗体的研发需要深入理解癌症血清学、蛋白质工程技术、作用与耐药机制，以及免疫系统与癌细胞间的相互作用。本文综述了从临床前研究到人体试验，通过靶点和抗体的迭代筛选，开发癌症患者抗体疗法所需的基本策略。

原文链接：

Antibody therapy of cancer