文章：

不断发展的靶向免疫疗法协同组合来对抗癌症

Evolving synergistic combinations of targeted immunotherapies to combat cancer

原文发布日期：2015-07-24

DOI: 10.1038/nrc3973

类型: Review Article

开放获取: 否

要点：

1. Clinical trials have validated immuno-oncology as a new pillar of anticancer therapy.
2. Combinations could involve two (or more) sequential or simultaneous immunotherapies, and/or immunotherapies in combination with conventional cancer therapies.
3. The programmed cell death protein 1 (PD1)–PD1 ligand 1 (PDL1) axis seems to be the most promising immuno-oncology target, and its blockade is likely to become the main foundation for combination strategies in the foreseeable future.
4. The paradigm of immuno-oncology combinations is to block PD1 and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) simultaneously; this blockade is synergistic and shows clinical benefit in patients with melanoma but has an increased frequency of immune-mediated, albeit clinically manageable, toxic effects.
5. Even if designing rational combinations that provide optimal benefit to patients with cancer is a challenging process, there are a number of different combination immuno-oncology therapies currently in development.

要点翻译：

1. 临床试验已证实免疫肿瘤学成为抗癌治疗的一个新支柱。
2. 联合治疗可能涉及两种（或多种）序贯或同步的免疫疗法，和/或免疫疗法与传统癌症治疗的结合。
3. 程序性细胞死亡蛋白1（PD1）–PD1配体1（PDL1）轴似乎是最有前景的免疫肿瘤学靶点，在可预见的未来，其阻断策略很可能成为联合治疗方案的主要基础。
4. 免疫肿瘤学联合治疗的范式是同时阻断PD1和细胞毒性T淋巴细胞相关抗原4（CTLA4）；这种阻断具有协同作用，在黑色素瘤患者中显示出临床益处，但免疫介导的毒性反应发生率增加，尽管这些毒性反应在临床上是可以控制的。
5. 尽管设计合理的联合方案以为癌症患者提供最佳疗效是一个具有挑战性的过程，但目前仍有多种不同的免疫肿瘤学联合疗法正在研发中。

英文摘要：

Immunotherapy has now been clinically validated as an effective treatment for many cancers. There is tremendous potential for synergistic combinations of immunotherapy agents and for combining immunotherapy agents with conventional cancer treatments. Clinical trials combining blockade of cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) may serve as a paradigm to guide future approaches to immuno-oncology combination therapy. In this Review, we discuss progress in the synergistic design of immune-targeting combination therapies and highlight the challenges involved in tailoring such strategies to provide maximal benefit to patients.

摘要翻译： 

免疫疗法现已在临床上被证实对多种癌症有效。免疫治疗药物之间，以及免疫治疗药物与传统癌症疗法之间，具有巨大的协同联合潜力。阻断细胞毒性T淋巴细胞相关抗原4（CTLA4）与程序性死亡蛋白1（PD1）的临床试验，可作为指导未来肿瘤免疫联合治疗策略的范例。本综述探讨了免疫靶向联合疗法在协同设计方面的进展，并强调了制定个体化策略以使患者获得最大益处的挑战。

原文链接：

Evolving synergistic combinations of targeted immunotherapies to combat cancer