Vacchelli Erika, Senovilla Laura, Eggermont Alexander, Fridman Wolf Hervé, Galon Jérôme, Zitvogel Laurence, Kroemer Guido, Galluzzi Lorenzo
Institut Gustave Roussy; Villejuif, France ; Université Paris-Sud/Paris XI; Le Kremlin-Bicêtre, France ; INSERM, U848; Villejuif, France.
Oncoimmunology. 2013 Mar 1;2(3):e23510. doi: 10.4161/onci.23510.
It is now clear that the immune system plays a critical role not only during oncogenesis and tumor progression, but also as established neoplastic lesions respond to therapy. Selected cytotoxic chemicals can indeed elicit immunogenic cell death, a functionally peculiar type of apoptosis that stimulates tumor-specific cognate immune responses. Such immunogenic chemotherapeutics include cyclophosphamide, doxorubicin and oxaliplatin (which are approved by FDA for the treatment of various hematological and solid malignancies), mitoxantrone (which is currently employed both as an anticancer agent and against multiple sclerosis) and patupilone (a microtubular poison in clinical development). One year ago, in the second issue of , we discussed the scientific rationale behind immunogenic chemotherapy and reviewed the status of recent clinical trials investigating the off-label use of cyclophosphamide, doxorubicin, oxaliplatin and mitoxantrone in cancer patients. Here, we summarize the latest developments in this area of clinical research, covering both high-impact studies that have been published during the last 13 months and clinical trials that have been initiated in the same period to assess the antineoplastic profile of immunogenic chemotherapeutics.
现在已经清楚,免疫系统不仅在肿瘤发生和肿瘤进展过程中发挥关键作用,而且在既定的肿瘤性病变对治疗产生反应时也发挥关键作用。某些细胞毒性化学物质确实能够引发免疫原性细胞死亡,这是一种功能特殊的细胞凋亡类型,可刺激肿瘤特异性同源免疫反应。这类具有免疫原性的化疗药物包括环磷酰胺、阿霉素和奥沙利铂(已获美国食品药品监督管理局批准用于治疗各种血液系统恶性肿瘤和实体恶性肿瘤)、米托蒽醌(目前既用作抗癌药物,也用于治疗多发性硬化症)以及帕土匹隆(一种处于临床开发阶段的微管毒素)。一年前,在《》的第二期,我们讨论了免疫原性化疗背后的科学原理,并综述了近期关于癌症患者使用环磷酰胺、阿霉素、奥沙利铂和米托蒽醌的非标签用药临床试验的情况。在此,我们总结该临床研究领域的最新进展,涵盖过去13个月内发表的具有重大影响的研究以及同期启动的旨在评估免疫原性化疗药物抗肿瘤特性的临床试验。