Periodic Reporting for period 1 - Melomanes (Combination therapy for the treatment of metastatic melanoma using magnetic nanoparticles)
Reporting period: 2023-03-01 to 2025-02-28
Cancer is the second leading cause of mortality in EU countries, after cardiovascular diseases, with cancer deaths estimated to be at 1.3 million in 2022. Every year, an increasing number of people are diagnosed with the disease, with the number of new cases reaching 2.7 million in 2022. Notably, Europe has a quarter of all cancer cases and less than 10% of the world’s population.
The fight against cancer operates in several key areas. First, the prevention of cancer can be achieved through the decrease of risk factors and the use of vaccines. Secondly, the early detection of all cancers greatly increases the chances for survivorship, so cancer screening is essential. Thirdly, the cancer diagnosis and treatments require more scientific research to offer hope for a cure and better survival rates.
One of the most worrisome cancers is metastatic melanoma, a skin cancer that spread to other parts of the body as it was not detected early enough. Its prognosis is poor, with a median survival of 6 to 9 months, and a 5-year survival rate of 22.5%. Metastatic melanoma is a hard-to-treat disease, as the current therapies have a limited efficacy. For promising immunotherapies of metastatic melanoma, such as chimeric antigen receptor (CAR)-T cells, the efficiency is limited by the low access to the tumour by the CAR-T cells. This is related to the physical barriers represented by cellular and non-cellular components of the tumour microenvironment.
MELOMANES is a training-by-research project that develops an innovative combined therapy to treat metastatic melanoma. The therapeutic strategy is to facilitate the infiltration of CAR-T cells by using magnetic nanoparticles to damage the tumour microenvironment, by magnetic and optic hyperthermia. The project aims at developing a proof of concept of the combined treatment for metastatic melanoma, while taking into account the safety, sustainability and ethical challenges.
The fight against cancer operates in several key areas. First, the prevention of cancer can be achieved through the decrease of risk factors and the use of vaccines. Secondly, the early detection of all cancers greatly increases the chances for survivorship, so cancer screening is essential. Thirdly, the cancer diagnosis and treatments require more scientific research to offer hope for a cure and better survival rates.
One of the most worrisome cancers is metastatic melanoma, a skin cancer that spread to other parts of the body as it was not detected early enough. Its prognosis is poor, with a median survival of 6 to 9 months, and a 5-year survival rate of 22.5%. Metastatic melanoma is a hard-to-treat disease, as the current therapies have a limited efficacy. For promising immunotherapies of metastatic melanoma, such as chimeric antigen receptor (CAR)-T cells, the efficiency is limited by the low access to the tumour by the CAR-T cells. This is related to the physical barriers represented by cellular and non-cellular components of the tumour microenvironment.
MELOMANES is a training-by-research project that develops an innovative combined therapy to treat metastatic melanoma. The therapeutic strategy is to facilitate the infiltration of CAR-T cells by using magnetic nanoparticles to damage the tumour microenvironment, by magnetic and optic hyperthermia. The project aims at developing a proof of concept of the combined treatment for metastatic melanoma, while taking into account the safety, sustainability and ethical challenges.
5 main lines of action have structured the work performed in MELOMANES so far:
- The doctoral researchers have performed the synthesis and functionalisation of magnetic nanoparticles endowed of properties for magnetic hyperthermia and photothermal therapy
- The doctoral researchers have assessed the nanoparticle safety and biocompatibility, and developed models for improved toxicity assessment of the nanoparticles.
- The doctoral researchers have built in vitro 3D models and in vivo melanoma murine models. The development of a melanoma-on-chip device is in progress. This microfluidic system, along with the in vitro and in vivo models, will allow evaluating the alteration of the tumour microenvironment using photothermal therapy and magnetic hyperthermia mediated by the nanoparticles, and assessing the infiltration of chimeric antigen receptor (CAR)-T cells into the tumour.
- The doctoral researchers have engineered T-cells, including CAR-T cells and T cell receptor (TCR)-T cells, able to eliminate melanoma cells.
- The doctoral researchers have developed an initial safe-and-sustainable-by-design framework tailored to the pharmaceutical sector, which will serve as a basis for the development of a more specific framework for nanomedicines. They have also developed a framework for responsible nanomedicine to embed the ethical concerns within research, development and innovation in nanomedicine.
- The doctoral researchers have performed the synthesis and functionalisation of magnetic nanoparticles endowed of properties for magnetic hyperthermia and photothermal therapy
- The doctoral researchers have assessed the nanoparticle safety and biocompatibility, and developed models for improved toxicity assessment of the nanoparticles.
- The doctoral researchers have built in vitro 3D models and in vivo melanoma murine models. The development of a melanoma-on-chip device is in progress. This microfluidic system, along with the in vitro and in vivo models, will allow evaluating the alteration of the tumour microenvironment using photothermal therapy and magnetic hyperthermia mediated by the nanoparticles, and assessing the infiltration of chimeric antigen receptor (CAR)-T cells into the tumour.
- The doctoral researchers have engineered T-cells, including CAR-T cells and T cell receptor (TCR)-T cells, able to eliminate melanoma cells.
- The doctoral researchers have developed an initial safe-and-sustainable-by-design framework tailored to the pharmaceutical sector, which will serve as a basis for the development of a more specific framework for nanomedicines. They have also developed a framework for responsible nanomedicine to embed the ethical concerns within research, development and innovation in nanomedicine.
An open-access validated and predictive machine learning/artificial intelligence model for the risk assessment of iron carbide nanoparticles has been developed.
To facilitate automation of high-throughput transcriptomics analyses and data interpretation, a dedicated open-source Shiny application has been developed, allowing to support reproducible, programmatic workflows for high-throughput transcriptomic data analysis.
Novel melanoma antigen-specific CAR-T cells and TCR-T cells have been produced.
It is expected that the MELOMANES project will lead to the proof-of-concept of the combined treatment for metastatic melanoma, using nanoparticles and CAR-T cells.
To facilitate automation of high-throughput transcriptomics analyses and data interpretation, a dedicated open-source Shiny application has been developed, allowing to support reproducible, programmatic workflows for high-throughput transcriptomic data analysis.
Novel melanoma antigen-specific CAR-T cells and TCR-T cells have been produced.
It is expected that the MELOMANES project will lead to the proof-of-concept of the combined treatment for metastatic melanoma, using nanoparticles and CAR-T cells.