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Advancing CAR T-cell therapy: BC scientist aims to improve therapy for patients with extranodal lymphoma

Immunotherapies, including CAR T-cell therapy, are highly promising new cancer treatments harnessing the body’s own immune system to fight cancer.

“There's so much excitement around CAR T-cell therapy and synthetic biology and for good reason. Clinically, it's been very effective,” says Dr. Laura Evgin, scientist at BC Cancer Research Institute (BCCRI) and assistant professor at The University of British Columbia. “However, it is still relatively immature and there are many patients who fail to respond.”

As a 2024 Terry Fox New Investigator awardee, Dr. Evgin will seek to understand why CAR T-cell therapy is less effective for patients with extranodal lymphoma—wherein the cancer is distributed beyond the lymph nodes—and test strategies for enhancing patient outcomes.

Dr. Evgin’s investigation will concentrate on T cells, critical components of the immune system responsible for identifying and eliminating a variety of infected or malignant cells. In CAR T-cell therapy, these immune cells are equipped with chimeric antigen receptors (CARs) to specifically target and kill cancer cells expressing the CD19 protein. This approach shows potential for minimizing harm to normal cells and reduces the adverse effects associated with traditional, more toxic, cancer therapies.

However, a significant challenge in CAR T-cell therapy is delivering these genetically engineered cancer-killing cells to “rural” cancers spread throughout the body.

To address this challenge, Dr. Evgin’s project will focus on three core objectives:

  1. Utilizing mouse models that mimic human lymphoma, her team will identify and compare the mechanisms underlying treatment failure in nodal (localized) and extranodal disease. This approach will allow them to observe CAR T-cell behaviour in intricate detail, which would not be possible through blood samples or human trials.
  2. With this knowledge, they will genetically engineer CAR T cells that are optimized to treat extranodal disease more effectively.
  3. Finally, they will perform a retrospective analysis of diagnostic images captured throughout the treatment of patients enrolled in the Canadian Led Immunotherapies in Cancer (CLIC) CAR T-cell clinical trial to gain further insight into the function of CAR T-cells at specific sites. In doing so, they hope to understand whether certain sites relapse so therapies may be designed to target those locations.

Throughout her project, she will be working closely with colleagues at BCCRI, including a Terry Fox Program Project Grant team (Modeling lymphoma evolution and clinical trajectory using multiomics) led by Dr. Christian Steidl, as well as the BCCRI and Ottawa Hospital Research Institute groups leading the trial.

“We have a real opportunity to better understand the mechanisms underlying CAR T-cell treatment failure so that we can identify those patients who will benefit the most from this type of therapy and develop superior products to treat those who likely wouldn’t respond,” says Dr. Evgin.