Cancer targeted by genome-editing reserach

Why do some patients undergoing cancer immunotherapy respond while others don't? How can the DNA-editing tool CRISPR improve these therapies? And once a patient is treated with CRISPR-modified immunotherapy, where do those cells go in the body?

These are questions Schulich School of Medicine & Dentistry professor John Ronald hopes to answer as part of a new research program funded by a National Institutes of Health (NIH) grant allowing his team to build new imaging tools to monitor a new class of cancer immunotherapies called CAR-T cells.

"CAR-T cells are already being used in patients to treat blood cancers and are being rapidly developed for other cancer types such as breast and brain cancer," Ronald said. "However, not all patients respond to this therapy and some patients can experience life-threatening side effects. Why some patients respond or don't and why some experience these side effects isn't known."

Cancer scientists globally are using the genome-editing tool CRISPR to alter CAR-T cell therapies to improve their cancer-killing potential. However, once the cells are injected into the body, tools for monitoring where they go and how they are behaving or misbehaving currently don't exist.

The goal of the NIH-funded research is to innovate new clinically relevant magnetic resonance imaging (MRI) and positron emission tomography (PET) technologies to monitor the fate of these CRISPR-edited CAR-T cells.

Ronald says their imaging technologies could provide the critical data needed to understand individual patient response by actually visualizing where these cells go within the body. "We hope this information will lead to improved management of individual cancer patients as well as the development of improved CAR-T cell formulations in the future."

As part of the grant, Ronald and his team will become part of NIH's Somatic Cell Genome Editing (SCGE) consortium, an international collection of interdisciplinary scientists, who are working on various aspects of genome editing.

"This opportunity allows us to interact with some of the pioneers in this relatively new field, which we hope will lead to future collaborations," Ronald said. "One of the main goals of SCGE is to develop a toolkit that will become available to the broader research community in the hope of reducing the cost and time to develop new genome editing therapies for a variety of diseases."

The first phase of this NIH grant will provide approximately $360,000 over the next two years, with potential for further funding as the project progresses.

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