With the support from a newly announced Terry Fox New Frontiers Program Project Grant, Madhuri Koti and her team will study how the immune system responds to cancer throughout the disease journey.
With the support from a newly announced Terry Fox New Frontiers Program Project Grant, Madhuri Koti and her team will study how the immune system responds to cancer throughout the disease journey.
More than 50 years ago, Queen's researchers led by Alvaro Morales (Professor Emeritus, Urology) made a groundbreaking discovery: a vaccine used to prevent tuberculosis could effectively boost the immune system to treat early-stage bladder cancer. Their innovative use of the Bacillus Calmette Guérin (BCG) vaccine became the global standard and remains one of the most successful immunotherapies to date. However, it only benefits about half of the patients. Now, a team led by Queen's researcher Madhuri Koti is trying to find out why.
Canada's fifth most common cancer
Bladder cancer ranks as the fifth most common cancer in Canada, with 12,300 new cases diagnosed in 2023 alone. Smokers, men, and older adults face the highest risk, and as Canada's population ages, the number of diagnoses is expected to increase.
Currently, the BCG vaccine is administered directly into a patient's bladder following surgical removal of a tumour, where it works to prevent tumour progression or recurrence and helps avoid the need for bladder removal.
"Unfortunately, this treatment is quite costly, resource intensive, and is unsuccessful for more than half of patients," says Dr. Koti, Associate Professor in Queen's Department of Biomedical and Molecular Sciences and principal investigator at the Sinclair Cancer Research Institute (SCRI), Queen's Health Sciences. "We want to identify early on which patients are unlikely to respond so they can be treated with alternative therapies."
Terry Fox Research Institute funding
With the support from a newly announced Terry Fox New Frontiers Program Project Grant, Dr. Koti and her team will study how the immune system responds to cancer throughout the disease journey.
They believe this approach will not only deepen our understanding of how bladder cancer recurs or progresses to advanced stages despite treatment with BCG, but also help identify unique characteristics in patient tumors that arise due to differences in each patient's immune system. By studying the interactions between cancer cells and the immune system, they hope to develop biomarkers that could guide new treatments for patients who don't respond to BCG immunotherapy.
This image shows a tumor with groups of 'smaller' immune cells (in multiple colours) as they approach but fail to eliminate 'larger' cancer cells (in blue). The funded projects aim to explore these complex interactions from multiple perspectives towards improving a patient's response to BCG immunotherapy. (Image provided by Dr. Madhuri Koti)
The $2.4 million multi-year funding will help advance three projects at the core of the team's work. The first, led by SCRI researchers David Berman and Lynne-Marie Postovit, will explore how bladder cancer cells adapt and resist treatment, by studying tumours prior to and during disease progression in patients who do not respond to BCG therapy.
The second project, led by Dr. Koti and Robert Siemens, will use advanced AI and imaging to identify immune related features in patient tumors that may predict disease outcome. Using patient blood samples, they will work with Queen's chemical engineers Carlos Escobedo and Laura Wells to develop a novel test for immune response monitoring that can be used during BCG therapy.
The third project, directed by SCRI researchers Charles Graham, Peter Greer, and Andrew Craig, will examine patients' immune cells in the blood and seek to identify features within them that distinguish patients who respond to treatment from those who do not.
SCRI researchers Amber Simpson and Tricia Cottrell will support all three projects, helping to analyze the data they collect using advanced computational analytics and infrastructure.
"The Terry Fox New Frontiers Program Project Grant enables us to unite our interdisciplinary research efforts, to strengthen national and international collaborations, and to build a world-class bladder cancer research program at the SCRI," Dr. Koti says. "On behalf of our team, I would like to thank the TFRI and all the donors who support their mission. Success in this competition is a result of real team effort and we're extremely honoured to be awarded this funding and to continue research on a treatment that started here at Queen's more than 50 years ago."
Training tomorrow's researchers
The funding will also help support training the next generation of researchers, including undergraduate, graduate, and postdoctoral level trainees. Over 15 trainees at various levels of their post-graduate training made significant contributions that led to the success of this grant, which will also help boost recruitment of newer graduate and postdoctoral fellows to the program.
"Our bladder cancer research program is unique in that it allows trainees to learn from each other's projects and apply that knowledge," Dr. Koti says. "This program will provide them with opportunities to engage with a multidisciplinary team of fundamental and clinician scientists, and to acquire the skills needed to carry this research forward, with the hope of reducing the incidence and recurrence of bladder cancer ultimately improving the lives of patients."
