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 immunotherapies has 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.

Development of credible non-animal technologies is necessary before well-established animal tests can be eliminated from drug discovery, chemicals testing and basic research. Miniature devices that replicate human organ function in the laboratory, so-called "Organs-on-Chips", have already been used in the race to discover new medicines to treat viral infections and lung disease. Organs-on-Chips hold promise for broader applications where they would provide superior alternatives to animal tests by better predicting the human response to new drugs. This project will overcome important barriers to the more widespread adoption of Organs-on-Chips in research laboratories around the world by using innovative manufacturing techniques to produce low cost devices that are highly intuitive to use. The availability of Organs-on-Chips to a broader community of scientists will accelerate research in this important field, leading to less animal testing and making participation in clinical trials much safer.

The SARS-CoV-2 (COVID-19) pandemic has been met with an unprecedented global response from the scientific and medical communities, to accelerate understanding and ultimately treatment and prophylaxis of the virus. An overwhelming need for new or re-purposed medicines and tools for their discovery exists. Currently, discovering and developing new medicines is a process spanning decades. New medicines require rigorous pre-clinical development prior to clinical trials with thousands of patients. Despite the rigor, new medicines often fail when taken to clinical trial. A large portion of this development is performed _in vivo-_ in animal models and while _in vivo_ testing has proved to be a valuable resource, the inherent differences across human and animals likely results in misrepresenting the effects of the medicines when translated to a human setting. New and innovate tools are therefore required to provide a more realistic representation of the human cell and tissue environments, enabling more accurate development of therapeutics. The team at CN Bio aims to develop a human 3D "organ-on-chip" lung cell culture model that more accurately reflects the human environment. To investigate the effects of SARS-CoV-2 in the lung we will use SARS-CoV-2 pseudoparticles, a reliable alternative to live virus. This system will also be used to investigate the effect of SARS-CoV-2 infection throughout the body by linking other organ systems including the liver and gut. We will use our state-of-the-art proprietary technology, the PhysioMimix system to meet these goals. This system is currently in commercial use for modelling the liver, and our in-house capabilities allows us to rapidly prototype, test and validated new cellular models. We will work in collaboration with academic, industrial and government partners to ensure this model is suitable to reflect the impact of SARS-CoV-2 infection. Ultimately, this system will enable researchers across the globe to investigate and understand SARS-CoV-2 infection and will allow for development of new medicines with improved accuracy and efficiency when reaching clinical stages. The technology, know-how and information obtained from this research will aid in the global fight against the spread of the virus.

NASH presents a significant unmet medical need in more economically developed nations, affecting up to 5% of the US population alone. There is currently no medical treatment for NASH, where the condition is a precursor to cirrhosis and hepatocellular carcinoma, conditions with very poor prognoses. One key limiting factor in the development of a treatment for NASH is a lack of suitable in vitro models. The project will produce a highly representative, medium throughput, 3D perfused model of NASH using both primary human and induced pluripotent stem cell derived hepatocytes, kupffer and stellate co-cultures. These models can be used in collaboration with industry to enable highly effective drug discovery studies and macrosteatotically relevant ADME/Toxicology studies.

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