In recent funding calls, IMI turned its attention to emerging cancer therapies, seeking better understanding of things like the effect of tumour microenvironment on immunotherapy success
Tumour-immune system interplay
A tumour is made up not only of a diverse population of cancer cells but also a mix of resident and infiltrating host cells and other elements collectively referred to as the tumour microenvironment. The progression of a tumour depends on how the cancer cells interact within this environment, and this interplay is a determining factor in how the tumour responds to treatment.
If we could understand more about the tumour microenvironment, we might be able to pinpoint who might benefit from some of the emerging immunotherapy treatments like immune checkpoint inhibitors. Despite showing promising results, this kind of therapy doesn’t work for everyone: we need biomarkers to select patients that might respond, as well as rationale for combining immune checkpoint inhibitors with conventional therapy.
The IMMUCAN project was launched in 2019 with the goal of analysing the tumour tissue, blood, stool, saliva, and clinical data from about 3,000 patients to hopefully better understand the mechanisms of resistance to current treatment (including immunotherapy) that would enable identification of new therapeutic targets and identify biomarkers that can tell us who is most likely to respond well to what treatment.
Video: the promise of CAR T-cell therapy
The big questions in new – and established – cancer treatments
Here's a brief summary of the other cancer-related questions that form the basis of IMI’s most recent calls for proposals and newly-launched projects.
How safe and effective are immunotherapy drugs? It’s hard to predict the how safe or effective immune therapies are before they are tested in humans because tests used early in drug development don’t reflect the full complexity of the human immune system, and they tend to be based on a healthy immune system. The imSAVAR project, launched in 2019, is creating tools to help figure out the potential safety or efficacy issues of these therapies in the early drug development stages.
How can we make T-cell therapies safer and more effective? T-cells are an important part of the immune system, and in recent years scientists have succeeded in creating ‘engineered’ T-cells designed specifically to fight cancers. However, it’s very hard to predict toxicity issues or to estimate accurately how well a treatment will work. Call 18 sought research teams who could deliver tools and markers that will improve our ability to make these predictions, as well as techniques to analyse the behaviour of T-cells in the body.
Why do some patients develop resistance to cancer drugs? Often, patients respond well to a drug before the cancer becomes resistant to it, and this drug resistance is a major cause of cancer mortality. The source of this resistance lies in rare cancer cells called ‘drug tolerant persister’ cells, or DTPs, which seem to survive treatment by altering the activity of certain genes. As part of call 20, IMI is looking to fund projects that will improve our understanding of DTPs, by developping tools to collect and analyse them and thereby identify new drug targets to overcome drug resistance.
Is proton therapy better than radiotherapy for treating certain cancers? Radiotherapy is one of the essential therapies for treating cancer patients, however the potential for causing side effects in surrounding organs is a limitation of this treatment modality.In contrast, proton therapy delivers a higher dose of radiation that is more focused on the tumour itself, limiting damage to other, healthy organs. Using oesophageal cancer as a case study, IMI’s latest call seeks to understand more about the best use-case for proton therapy.
How should we measure subjective outcomes in cancer trials? Many measures of disease (and disease outcomes) are based largely on input from clinicians and don’t fully capture patients’ experiences and the impact on their quality of life. Call 18 sought to fund research that would establish ‘health outcomes observatories’ that would make it easy for patients to report their health outcomes and experience of healthcare. The observatories, to be initially established in the areas of diabetes, inflammatory bowel disease, and cancer - would consist of technologies and a platform for gathering data, along with standards and ethical approaches.