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Project seeks new way to assess immunotherapy effectiveness

Nov. 7, 2019, 10:27 AM

 

by Krystyna Barnard

GE Healthcare has awarded researchers in the Vanderbilt University Institute of Imaging Science (VUIIS) $2.5 million in funding to develop a positron emission tomography (PET) tracer that will determine the effectiveness of immunotherapy in patients early in their treatment course.

The goal of the project, led by Charles Manning, PhD, professor of Radiology and Radiological Sciences, is to develop a novel PET imaging tracer that will detect activated T-cells in tumors and other organs before and immediately following therapy.

Charles Manning, PhD, and colleagues are working to improve the effectiveness of immunotherapies earlier in treatment.
Charles Manning, PhD, and colleagues are working to improve the effectiveness of immunotherapies earlier in treatment. (photo by John Russell)

“Despite major advances in immunotherapy for the treatment of cancer, quantitative biomarkers suitable to identify patients likely to respond to immunotherapy and to predict response, or lack thereof, early are deficient,” said Manning.

While the project’s primary aim is to evaluate immune cells’ response in tumors, Manning says the new class of tracers to be developed may also predict toxicity of immunotherapy in critical organs such as the heart and liver.

Currently, no contemporary F-18 PET tracers with CD8+ expression exist to aid in that discovery.

Funding awarded for the project will allow researchers to manipulate radiopharmaceuticals in the form of small molecules paired with F-18 that focus on CD8+, among other promising immune cell targets.

“The results of this project are expected to be a launching pad for first-in-human PET imaging studies using a novel PET tracer. We anticipate incorporating these tracers into larger clinical trials to accentuate therapy studies,” said Manning.

Ultimately, the development of these tracers will allow researchers the opportunity to better understand how immunotherapy works in cancer. It will also enable patients to discontinue treatment that is unlikely to be successful before they experience the undesirable side effects and potential costs of that treatment.

“With a better understanding of mechanisms that drive immunotherapy, it may be easier to match patients with this treatment and/or rationale combinations,” said Manning. “It will also allow their physician to rapidly consider alternative therapies that might be more productive.”

Research for this project is supported by colleagues at Vanderbilt University Medical Center, Vanderbilt University and VUIIS. Radio tracer discovery and PET imaging studies in Manning’s lab are being complemented by critical immunology and mouse modeling studies performed in the labs of Jeff Rathmell, PhD, and Ann Richmond, PhD.

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