Changing the landscape of treatment for chronic diseases

    Groundbreaking research could help prevent immune system “exhaustion” against diseases like cancer and HIV.

    By Cheryl Deslaurier on August 9, 2016

    Shokrollah Elahi from the University of Alberta’s Faculty of Medicine & Dentistry wants to change the landscape of how chronic diseases like HIV, HCV and cancer are treated. And with help from new funding by the Canadian Institutes of Health Research (CIHR), his groundbreaking research has the potential to do it.

    A certain immune cell type referred to as killer T cells (cytotoxic T lymphocytes) play an important role in controlling chronic viral infections and cancer. When someone has a chronic viral infection such as HIV, HCV or cancer, killer T cells receive persistent signals from the viral and tumour antigens or inflammation.

    This is often associated with deteriorating function in the killer T cells, a state called “exhaustion.” These cells become dysfunctional and unable to eliminate infected cells and tumour cells in the course of chronic infections and cancer.

    So far, Elahi’s research has shown that a rare group of HIV-infected individuals called “long-term non-progressors’’ have natural protective immunity because their killer T cells avoid immune exhaustion.

    “Our goal with the research is to better understand the underlying mechanism of avoiding immune exhaustion in this rare group of HIV-infected individuals in order to prevent or reverse the immune exhaustion and allow the immune system to fight the chronic infections and cancer,” says Elahi, principal investigator and professor at the faculty. “We need to better understand the mechanism leading to killer T cells exhaustion and how this can be prevented.”

    His group discovered that certain killer T cells are genetically different in HIV controllers. Therefore, the killer T cells continue to function at a high level and destroy HIV-infected cells to ensure that the virus cannot reproduce to the extent that is associated with HIV progression. His team is building on these observations to investigate the complex series of signalling events between components of the human immune system that maintain killer T cells fully functional. This knowledge will be essential for developing novel immunotherapy methods targeting killer T cells.

    Elahi says that if they can change the behaviour of the killer T cells and jump-start the immune system to fight the virus or tumour, then they are making great progress.

    With $1.1 million in Foundation Grant funding from CIHR, Elahi’s group will perform a wide range of experiments to understand how T killer cells become dysfunctional in HIV, HCV and cancer and how this exhaustion can be prevented or reversed to develop new immunotherapy drugs.

    “We hope to identify and develop innovative and non-traditional immune-based therapies to allow killer T cells to stay protective and kill infected cells and cancer cells.”

    More CIHR Foundation Grants for UAlberta

    Elahi’s team was among six research groups at the U of A to receive more than $13 million in Foundation Grants from the Canadian Institutes of Health Research (CIHR):

    • Christian Beaulieu received $1.4 million to advance MRI technology for better diagnosis of conditions such as stroke and better understanding of brain development.
    • Patrick MacDonald received $2.2 million to further his world-leading research into the function of insulin-producing islet cells, which could lead to new treatments for diabetes.
    • Evangelos Michelakis received $3.9 million for his research on mitochondria, the “power plants” that fuel cells, to better understand how malfunctioning mitochondria lead to diseases such as pulmonary hypertension.
    • Shannon Scott and Lisa Hartling received $2.5 million to develop evidence-based tools for improving children’s health care by actively involving parents. This work could help reduce emergency department visits for ailments that could be better treated in other settings or at home.
    • David Wishart received $2.1 million to use the latest techniques in artificial intelligence to automatically harvest and identity vast amounts of data and learn from that data. This work will greatly accelerate discovery of new drugs, enable better diagnostics and help predict who is at risk of developing diseases like cancer, heart disease and diabetes.