Current clinical trials testing combinations of immunotherapy and radiation.
Current clinical trials testing combinations of immunotherapy and radiation.
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DOI：
10.1016/j.semradonc.2014.07.003
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发表时间：
2015-01
影响因子：
3.5
通讯作者：
Formenti S
中科院分区：
文献类型：
--
作者：
Crittenden M;Kohrt H;Levy R;Jones J;Camphausen K;Dicker A;Demaria S;Formenti S
电离辐射与免疫疗法成功结合的临床前证据激发了将这些结果转化为临床的测试。有趣的是，临床前工作一致地预测了临床试验中遇到的反应。第一个例子来自于2001年开始的一项原理验证试验，该试验测试了作用于抗原呈递细胞的生长因子改善辐射释放的肿瘤抗原呈递并诱导体外效应的概念。在转移性实体瘤患者的转移部位放疗期间给予粒细胞-巨噬细胞集落刺激因子，以翻译在细胞因子FLT-3L和放疗治疗的小鼠同基因乳腺癌模型中获得的证据。随后疫苗和免疫检查点抑制剂的临床可用性引发了一波将它们与放疗联合试验的热情。本报告描述了正在进行的临床试验的例子。重要的是，这些试验包括对入组患者进行仔细的免疫监测，并将产生有关在不同疾病环境下放射联合各种免疫调节剂的免疫原性效应的重要数据。这些研究的结果为放疗作为免疫治疗的辅助手段建立了一个证据平台，并促进了放射肿瘤学这一新兴领域的发展。
Preclinical evidence of successful combinations of ionizing radiation with immunotherapy has inspired testing the translation of these results to the clinic. Interestingly, the preclinical work has consistently predicted the responses encountered in clinical trials. The first example came from a proof-of-principle trial started in 2001 that tested the concept that growth factors acting on antigen-presenting cells improve presentation of tumor antigens released by radiation and induce an abscopal effect. Granulocyte-macrophage colony-stimulating factor was administered during radiotherapy to a metastatic site in patients with metastatic solid tumors to translate evidence obtained in a murine model of syngeneic mammary carcinoma treated with cytokine FLT-3L and radiation. Subsequent clinical availability of vaccines and immune checkpoint inhibitors has triggered a wave of enthusiasm for testing them in combination with radiotherapy. Examples of ongoing clinical trials are described in this report. Importantly, these trials include careful immune monitoring of the patients enrolled and will generate important data about the proimmunogenic effects of radiation in combination with a variety of immune modulators in different disease settings. Results of these studies are building a platform of evidence for radiotherapy as an adjuvant to immunotherapy and encourage the growth of this novel field of radiation oncology.