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Research Highlight | July 01, 2018

MCC sub-project looks to identify biomarkers that could predict success of immunotherapy for leukemia patients

A group of cancer investigators from some of the top research institutions in Montreal have come together to launch a groundbreaking project focused on making immunotherapy, a promising form of cancer treatment, more effective for patients with leukemia.

The team, which is working under the umbrella of the TFRI-led Montreal Cancer Consortium (MCC) and is led by Dr. Jean-Sébastien Delisle (Centre de Recherche Hôpital Maisonneuve-Rosemont), is hoping to do this by searching for genetic signatures in the DNA of leukemia patients that could predict how the immune system will interact with cancerous cells during different treatments.

“We know that some people with leukemia respond spectacularly well to immunotherapy, while others show absolutely no response at all, but the reasons why this happens are completely unknown,” says Dr. Delisle. “We hope this project can shed light on that and help us understand how to use immunotherapy in a more precise way.”

To search for these biomarkers, the team will gather samples from leukemia patients who have received a form of immunotherapy known as allogenic bone marrow transplants and sequence their genome and transcriptome to see if there are any unique signatures that could help predict if the treatment will be a success or if the disease will relapse.

They will then run a separate trial using something known as PD1 blockade to see if the immune environment in the marrow evolves during treatment, which could shed more light on the interplay between the immune system and leukemia.

A third part of the project will build on the results gathered in the first two parts of the study and use the new biomarkers to try to develop potential antigens that could target these genetic signatures and make leukemia cells more vulnerable to immunotherapy.

“These approaches are brand new and address a question that no one has really tried to answer before: ‘How do leukemia and immune cells interact during various treatments?’” explains Dr. Delisle. “We won’t be able to do this with 100 patients, but if we show that this pipeline can work on a handful of patients, it will enable several interesting things for the future, where we will have a fairly comprehensive view of how leukemia and the immune system intersect. 

An unmet need

Using biomarkers to determine as early as possible if immunotherapy will be the right course of action for patients with leukemia could help increase chances of survival for patients.

According to Dr. Delisle, treating a leukemia where the burden of disease is low, is easier than treating a full-blown relapse, which occurs in around 50 per cent of cases.

“If we could identify a genetic signature or a cell characteristic that will predict if a relapse will occur within the next few months, we can start acting on it immediately,” he says. “Currently, our line of conduct is to give them the transplant and wait and see. This approach is adequate, and we do cure a lot of people, but it is probably not the best way to serve some subset of patients that are more likely to relapse.”

By identifying the biomarkers and creating antigens that target them, the team will not only create a unique pipeline that could bring hope to patients with deadly blood cancers, it may help the public health system save millions of dollars, by creating cost-saving treatment plans that are more precise and effective.

“This project could have far-reaching applications in terms of resource allocation, treatment design, treatment algorithms,” says Dr. Delisle. “It’s something brand new, especially for Montreal, so it’s making all the researchers go a bit outside of our comfort zone.  Without an initiative like the MCC and leadership from the Terry Fox Research Institute encouraging this form of research, I don`t think it would have happened.”