Two collaborative projects led by the Luxembourg Institute of Health (LIH), recently approved for funding from the European Union (EU), will address new strategies related to cancer immunotherapy.
In spite of its enormous therapeutic potential to treat cancer, immunotherapy remains successful only in a limited number of patients. New strategies are required to define which patients may benefit from cancer immunotherapy and determine which innovative molecules, given in combination, could maximise its effectiveness. These two LIH collaborative projects will tackle these aspects with the aim of bringing innovative cancer immunotherapy to standard clinical practice sooner.
Despite the clinical use of various conventional treatments (such as chemotherapy, radiotherapy and targeted therapy), cancer is still reported as the second cause of death in Europe, with more than 1.9 million deaths in 2020. Over the past few years, cancer immunotherapy has emerged as a revolutionary alternative treatment approach to treat highly aggressive cancers for which conventional therapies have failed. In contrast to conventional therapies, cancer immunotherapy uses the patient's own immune system to fight cancer by awakening specialised immune cells to attack cancer cells. Although immunotherapy has rapidly gained significant interest for cancer treatment, clinical data showed that the impressive long-term survival benefit, achieved by immunotherapy, is only present in a minority of patients, while the majority of them reaped a short-term benefit or no benefit at all.
To extend the benefit of cancer immunotherapies, many clinical trials have focused on combining them with other available cancer immunotherapies. Despite several clinical trials undertaken to assess such combinations, the therapeutic benefit of significant number of them was disappointing and did not meet clinical expectations. Indeed, the combination of several immunotherapies to extensively boost the immune system has the potential to disrupt itsfinely tuned balance and enhance the risk of triggering autoimmune diseases. These side effects, combined with a lack of adequate biomarkers to predict the response to cancer immunotherapy, makes such combinatorial strategies questionable.
In this context, Dr Bassam Janji, head of the Tumor Immunotherapy and Microenvironment (TIME) research group at the Department of Cancer Research of the LIH, has teamed up with prominent biotech companies, Cytovation in Norway, and AC BioScience in Switzerland, as well as the leading European cancer centre Gustave Roussy in France, in two pioneering projects that aim to expand the versatility of cancer immunotherapy.
Based on promising phase one clinical data and powered by the collaboration with Cytovation, the PreCyse project will test the therapeutic benefit of immunotherapy based on immune checkpoint inhibitors, agents that can help the body’s immune system recognise and attack cancerous cells, in combination with an innovative molecule that can specifically target tumour cells.
"The net outcome of PreCyse project is to bring innovative combinatorial immunotherapy into clinical practice and define reliable biomarkers that guide the stratification of patients that would benefit from it", explained Dr Janji. "We hope that this pioneering combination will bring a turnaround in immunotherapy-based cancer treatment, which would create tremendous enthusiasm in anticancer care".
Similarly, the C2I project aims to bring alternative anti-cancer molecules that could improve the effectiveness of immune checkpoint inhibitors to clinical trial stage. Based on synergistic cooperation between AC BioScience, TIME group and the Gustave Roussy centre, this project will establish the preclinical proof-of-concept and assess novel immunotherapy approaches based on combining molecules allowing better presentation of cancer cells to the immune system.
"This combinatorial approach could lead to new therapeutic options, with the ultimate aim to expand the use of current immunotherapy treatments to a large number of cancer patients", added Dr Janji. "At the LIH, we work to break the boundaries of traditional medicine. The success of immunotherapy in the treatment of patients with incurable and advanced tumours is in the process of revolutionising the way we treat cancers. By establishing robust biomarkers, immunotherapy can provide personalised solutions instead of the traditional one-size-fits-all approach of standard medicine, and therefore encompass all the values of precision medicine".
He concluded: "We hope that by combining our novel agents with available cancer immunotherapy, we will be able to simultaneously and specifically directly attack the tumour cells and activate the immune system. Our approach could finally make cancer immunotherapy available to a wider range of patients".
