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Luxembourg National Research Fund

First project funded in collaboration agreement between FNR and Fondation Cancer

The FNR and Fondation Cancer have concluded a collaboration agreement to develop and intensify their cooperation in order to support high-level cancer research projects. In the scope of the FNR’s CORE programme, the FNR and Fondation Cancer are jointly funding a cancer immunotherapy research project at the Luxembourg Institute of Health (LIH).

Left to right: Maiti Lommel (Fondation Cancer); Dr Guy Berchem (LIH / CHL); Lucienne Thommes (Director Fondation Cancer); Dr Bassam Janji (LIH); Sean Sapcariu (FNR); Marc Schiltz (Secretary General FNR) – copyright: Fondation Cancer

On Wednesday, 16 January, Lucienne Thommes, Director of Fondation Cancer, presented a cheque for 213,125 EUR to researchers Dr Bassam Janji and Dr Guy Berchem in the presence of Marc Schiltz, Secretary General of the FNR. The FNR matches the Fondation Cancer amount and has also committed 213,125 EUR to the project in the 2018 CORE Call.

The project ‘Improving T-cell and Macrophage Immune checkpoint blockades, combining autophagy inhibitors (COMBATIC)’ aims to improve the effectiveness of immune checkpoint inhibitors in patients who have not previously been eligible for immunotherapy.

The FNR and Fondation Cancer have a long-standing collaboration already: over the years, the FNR has assisted the charity in its review process, to help ensure a high quality of projects. As part of the new collaboration agreement, researchers submitting proposals to the FNR’s 2019 CORE Call can specify whether their project should be considered for Fondation Cancer co-funding. Applicants have to provide evidence that these cancer projects are in line with the CORE domain of ‘Biomedical sciences’ and comply with the topics of the Plan Cancer.

Utilising the immune system to attack cancer cells

Unlike other cancer treatment strategies, immunotherapy is a revolutionary treatment that does not directly target the tumour, but acts primarily on the cancer patient’s immune system to enable it to recognise and attack cancer cells. Indeed, cancer cells manage to thwart the body’s defence mechanisms so that they are not recognised by immune cells as abnormal cells: they acquire shields, called immune checkpoints, which protect them and neutralise immune cells.

Immunotherapy – effective against different types of cancers

Immunotherapy, particularly those based on immune checkpoint inhibitors, has led to considerable progress. A durable response has been achieved in patients with metastatic skin melanoma (skin cancer) resistant to standardised treatments such as chemotherapy. Immunotherapy has also yielded very encouraging results for the treatment of lung cancer and relapsing Hodgkin’s lymphoma. The results are also very promising in some ear/nose/throat (ENT), colon, bladder, kidney and ovarian cancers. The results of immunotherapy treatment for breast cancer are not yet equal to those obtained for lung, melanoma or bladder cancer.

A real therapeutic feat on certain patients

However, the full and sustained efficacy of immunotherapy is limited to a proportion of cancer patients. Thus, in the case of melanoma, only 38% of cases benefit from a complete and lasting cure, while nearly 60% of patients derive no therapeutic benefit from it.

It is currently well established that patients with tumours that are poorly or not infiltrated by immune cells, called “deserted tumours” or “cold tumours”, do not benefit from any therapeutic advantage. In contrast, patients with tumours pre-infiltrated by immune cells, called “hot tumours” or “inflamed tumours”, generally benefit from a sustained immune response. Thus, this therapy can be particularly effective in awakening sleeping immune cells and/or strengthening those that are exhausted in warm, pre-infiltrated tumours.

In recent years, the Tumor Microenvironment research team at the Laboratory of Experimental Cancer Research, led by Drs. Bassam Janji and Guy Berchem of LIH, has launched a vast research program on immunotherapy aimed at improving the efficacy of immune checkpoint inhibitors, particularly in patients with cold tumours that are not eligible for this treatment.

Their pioneering research has identified a target in tumours whose blocking allows the immune landscape of cold tumours to be reprogrammed. This reprogramming consists in inducing a massive infiltration of immune cells and thus making them sensitive to immunotherapy based on immune checkpoint inhibitors.

Reprogramming the tumour immune landscape to improve immunotherapy treatment

The COMBATIC project aims to evaluate the ability of pharmacological molecules to induce pre-infiltration of immune cells in experimental preclinical models of melanoma and colon cancer that are not eligible for immunotherapy. The project also plans to test the therapeutic benefit of a combination of these molecules with immune checkpoint inhibitors.

The ultimate goal of this project is to provide a therapeutic strategy capable of reprogramming the immune landscape from cold tumours not eligible for immunotherapy to warm tumours pre-infiltrated by immune cells.

These immune cells infiltrating reprogrammed tumours will be able to act against cancer cells under the effect of immunotherapy.

Although this project is currently in the pre-clinical phase, it will provide proof of concept for the clinical development of future drugs and pave the way for a major advance in immunotherapy for a wider range of cancer patients.

In this context, the FNR and the Cancer Foundation have decided to finance this large-scale and highly innovative research project, which could ultimately have a major therapeutic impact on cancer patients.

Watch Bassam Janji speak about his research and the new project in a short video by Fondation Cancer (French only)