文章：

构建更好的单克隆抗体治疗方法

Building better monoclonal antibody-based therapeutics

原文发布日期：2015-05-22

DOI: 10.1038/nrc3930

类型: Review Article

开放获取: 否

要点：

1. Monoclonal antibody (mAb)-based therapeutics are now standard in the treatment of cancer, and the numbers and varieties of clinically applicable mAb-based approaches continue to grow.
2. Effective mAb-based treatments of cancer include directly targeting the cancer, altering the host response to the cancer, delivering cytotoxic moieties to the cancer and retargeting T cells towards the cancer.
3. mAb-based treatments that directly target the cancer mediate their effects through direct signalling, antibody-dependent cellular cytotoxicity and complement-mediated lysis. Differentiating which of these mechanisms is most important for a given mAb can be difficult but is important when working to identify better mAb-based treatments.
4. mAb-based treatments that alter the host response can alter tumour angiogenesis or the T cell response through T cell checkpoint blockade. Checkpoint-blockade mAbs are showing particular promise.
5. mAb-based treatments that deliver cytotoxic agents to the cancer include radioimmunotherapy and antibody–drug conjugates (ADCs). ADCs are complex because of the need to match the target cancer to the right mAb, linker and drug, but early results are promising and many new ADCs are in development.
6. mAb-based treatments that retarget T cells towards cancer include bispecific antibodies and chimeric antigen receptor T cells. Both approaches are logistically challenging but have demonstrated exciting early results, particularly in B cell malignancies.
7. Each of these approaches has advantages and disadvantages that need to be considered in their development and evaluation.
8. Rapid progress is taking place in the development of new agents and the testing of new approaches, both alone and in combination, in each of these areas.

要点翻译：

1. 基于单克隆抗体（mAb）的疗法已成为癌症治疗的标准方案，其临床适用方法的数量与种类持续增长。
2. 有效的单抗癌症治疗策略包括：直接靶向癌细胞、改变宿主对癌症的应答、向癌细胞递送细胞毒性分子、以及重定向T细胞攻击癌细胞。
3. 直接靶向癌细胞的单抗疗法通过直接信号传导、抗体依赖性细胞毒性作用和补体介导的溶瘤效应发挥作用。虽然确定哪种机制对特定单抗最为关键具有一定难度，但这对于研发更优质的单抗疗法至关重要。
4. 调节宿主应答的单抗疗法可通过T细胞检查点阻断改变肿瘤血管生成或T细胞反应。检查点阻断单抗已显示出显著应用前景。
5. 向癌细胞递送细胞毒性药物的单抗疗法包括放射免疫疗法和抗体-药物偶联物（ADCs）。ADCs因需精准匹配靶点癌细胞与单抗、连接链及药物而设计复杂，但早期研究成果显著，目前有多种新型ADCs处于研发阶段。
6. 重定向T细胞攻击癌细胞的单抗疗法涵盖双特异性抗体和嵌合抗原受体T细胞。这两种方法在实施层面均存在挑战，但已展现出令人振奋的早期疗效，尤其在B细胞恶性肿瘤治疗中。
7. 每种治疗策略在研发与评估过程中均需权衡其独特优势与局限性。
8. 当前在所有上述领域，新型药物的研发和创新疗法的测试（包括单药与联合方案）均取得快速进展。

英文摘要：

For 20 years, monoclonal antibodies (mAbs) have been a standard component of cancer therapy, but there is still much room for improvement. Efforts continue to build better cancer therapeutics based on mAbs. Anticancer mAbs function through various mechanisms, including directly targeting the malignant cells, modifying the host response, delivering cytotoxic moieties and retargeting cellular immunity towards the malignant cells. Characteristics of mAbs that affect their efficacy include antigen specificity, overall structure, affinity for the target antigen and how a mAb component is incorporated into a construct that can trigger target cell death. This Review discusses the various approaches to using mAb-based therapeutics to treat cancer and the strategies used to take advantage of the unique potential of each approach, and provides examples of current mAb-based treatments.

摘要翻译： 

20年来，单克隆抗体（mAbs）一直是癌症治疗的标准组成部分，但仍有很大的改进空间。人们仍在继续努力，以mAbs为基础构建更好的癌症治疗药物。抗癌mAbs通过多种机制发挥作用，包括直接靶向恶性细胞、调节宿主反应、递送细胞毒性部分以及将细胞免疫重新定向至恶性细胞。影响mAbs效力的特征包括抗原特异性、整体结构、对目标抗原的亲和力，以及如何将mAb组分整合到能够触发目标细胞死亡的构建体中。本综述探讨了使用基于mAb的治疗药物治疗癌症的各种方法，以及利用每种方法独特潜力的策略，并提供了当前基于mAb的治疗实例。

原文链接：

Building better monoclonal antibody-based therapeutics