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Optimizing immunotherapy to improve outcomes for patients with high-risk leukemia

Acute lymphoblastic leukemia (ALL) is a type of cancer that develops in the bone marrow and invades the blood. Because it is acute, it progresses rapidly and can be fatal within months if not treated.

“Despite improvements in therapy, these cancers often return, with many patients succumbing to the disease,” says Dr. Anastasia Tikhonova, scientist at the Princess Margaret Cancer Centre.

“Patients also experience significant side-effects as a result of current therapies, so we really need therapies that are less toxic and more effective to reduce relapse and improve the quality of life for those patients who remain cancer-free.”

2024 Terry Fox New Investigator awardee Dr. Tikhonova will spend the next three years studying this aggressive cancer to understand why current treatments fail and aim to develop gentler, more effective approaches.

“Because this blood cancer is quite different from patient to patient, the same therapy cannot be applied to everyone. So, we want to understand how this disease differs from one patient to another, and how this links to each patient’s immune response,” she says.

By performing a comprehensive analysis investigating the behaviour of immune cells in the bone marrow of patients with ALL, she aims to understand why some types of this disease trigger a strong immune response while others do not. This understanding will help inform potential approaches to immunotherapy.

Immunotherapy is a major advancement in cancer care that leverages the patient’s own immune system to fight cancer, reducing both the toxicity of treatment and the associated side-effects. However, immunotherapy is currently ineffective for treating patients with T-lineage ALL—a subtype that occurs due to the uncontrolled growth of T cells in the bone marrow.

There are two key barriers hindering the success of immunotherapy for T-lineage ALL. Firstly, targeting the abnormal, or leukemic, T-cells poses difficulty without harming the body’s healthy T-cells, a vital component of our immune systems. Secondly, there are gaps in our understanding of how cytotoxic T cells interact with leukemia cells in the bone marrow, the site of disease progression.

“We hope that gaining this understanding will allow us to generate innovative treatments to target this disease in a more personalized manner, ultimately saving and improving the lives of affected patients,” says Dr. Tikhonova.