Combination Therapy for the Treatment of Metastatic MELanOma Using MAgnetic NanoparticlES

转移性黑色素瘤是一种难以治疗的疾病，它仍然是最令人担忧的癌症之一。迫切需要改进目前疗效有限的治疗方法（化疗、放疗）。单一疗法不能有效地治疗转移性黑色素瘤，因此联合治疗成为有效根除所有癌细胞的必要手段。最近，免疫疗法的发展显示出了希望，特别是嵌合抗原受体(CAR)-T细胞。然而，肿瘤微环境的细胞和非细胞成分所代表的物理障碍，加上肿瘤血管系统异常和间质液压力高，阻碍了CAR-T细胞的有效肿瘤浸润。在此背景下，由于有18个合作伙伴（包括10个非学术合作伙伴）组成的网络，MELOMANES旨在培训博士研究人员开发一种联合疗法，利用磁性纳米颗粒的特性，通过磁性和光学热疗诱导肿瘤微环境的损伤，以促进CAR-T细胞的浸润。这种结合热疗和免疫疗法的治疗方法是通用的，因为它也可以应用于其他类型的实体瘤。博士研究人员的研究和可转移培训将在高度跨学科、跨部门和国际的环境中进行。除了获得与研究项目相关的技能外，他们还将接受开放科学、沟通与传播、负责任的研究与创新、循环经济、伦理、数据管理、创业、市场营销、知识产权和研究中的性别维度方面的培训。他们的能力将通过认证和资格考试得到验证，使新一代高技能的博士研究人员能够在纳米医学多学科领域接受高水平的培训。

Metastatic melanoma is a hard-to-treat disease and it remains as one of the most worrisome cancer. There is an urgent need to improve the current therapies (chemotherapy, radiotherapy) that have a limited efficacy. A single therapy is not efficient to tackle metastatic melanoma and a combination of therapies is thus emerging as a necessity to efficiently eradicate all cancer cells. Recently, the development of immunotherapieshas shown promises, in particular chimeric antigen receptor (CAR)-T cells. Nevertheless, the physical barriers represented by cellular and noncellular components of the tumor microenvironment combined to the abnormal tumor vasculature and high interstitial fluid pressure, hamper an efficient tumour infiltration of CAR-T cells. In this context, thanks to a network of 18 partners (including 10 non-academic partners), MELOMANES aims to train doctoral researchers for the development of a combined therapy exploiting the properties of magnetic nanoparticles to induce damage on the tumor microenvironment by magnetic and optic hyperthermia in order to facilitate the infiltration of CAR-T cells. This therapeutic approach combining hyperthermia and immunotherapy is versatile, as it could be also applied to other types of solid tumors. Research and transferable training of the doctoral researchers will be performed in a highly interdisciplinary, intersectoral, and international environment. In addition to acquiring skills related to the research project, they will be trained also in open science, communication and dissemination, responsible research and innovation, circular economy, ethics, data management, entrepreneurship, marketing, intellectual property, and gender dimension in research. Their competences will be validated through certification and qualification examination, allowing a new generation of highly skilled doctoral researchers to emerge with a high-level training in particular in the multidisciplinary field of nanomedicine.