Institute of Clinical Physiology, CNR, Pisa, Italy.
Oncogenomics Unit, Core Research Laboratory, ISPRO, Pisa, Italy.
Oncogene. 2019 May;38(19):3756-3762. doi: 10.1038/s41388-019-0681-1. Epub 2019 Jan 21.
Attenuated Listeria monocytogenes (Lm-LLO) represents a valuable anticancer vaccine and drug delivery platform. Here we show that in vitro Lm-LLO causes ROS production and, in turn, apoptotic killing of a wide variety of melanoma cells, irrespectively of their stage, mutational status, sensitivity to BRAF inhibitors or degree of stemness. We also show that, when administered in the therapeutic setting to Braf/Pten genetically engineered mice, Lm-LLO causes a strong decrease in the size and volume of primary melanoma tumors, as well as a reduction of the metastatic burden. At the molecular level, we confirm that the anti-melanoma activity exerted in vivo by Lm-LLO depends also on its ability to potentiate the immune response of the organism against the infected tumor. Our data pave the way to the preclinical testing of listeria-based immunotherapeutic strategies against metastatic melanoma, using a genetically engineered mouse rather than xenograft models.
减毒李斯特菌 (Lm-LLO) 是一种有价值的抗癌疫苗和药物递送平台。在这里，我们表明 Lm-LLO 在体外会引起 ROS 的产生，进而导致各种黑色素瘤细胞的凋亡，而与它们的阶段、突变状态、对 BRAF 抑制剂的敏感性或干性程度无关。我们还表明，当在治疗环境中给予 Braf/Pten 基因工程小鼠时，Lm-LLO 会导致原发性黑色素瘤肿瘤的大小和体积明显减小，并减少转移负担。在分子水平上，我们证实 Lm-LLO 在体内发挥的抗黑色素瘤活性也取决于其增强机体对受感染肿瘤的免疫反应的能力。我们的数据为使用基因工程小鼠而不是异种移植模型对转移性黑色素瘤的李斯特菌免疫治疗策略进行临床前测试铺平了道路。
