Nav: Home

New imaging method may predict immunotherapy response early

May 01, 2017

Bottom Line: A noninvasive PET imaging method that measures granzyme B, a protein released by immune cells to kill cancer cells, was able to distinguish mouse and human tumors that responded to immune checkpoint inhibitors from those that did not respond early in the course of treatment.

Journal in Which the Study was Published: Cancer Research, a journal of the American Association for Cancer Research.

Author: Umar Mahmood, MD, PhD, professor of radiology at Harvard Medical School and director of the Division of Precision Medicine at Athinoula A. Martinos Center for Biomedical Imaging in Massachusetts General Hospital (MGH), Boston.

Background: Although immunotherapies, such as checkpoint inhibitors, have revolutionized cancer treatment, they only work in a minority of patients, which means that most patients receiving this treatment will not benefit but still have the increased risk of side effects, besides losing time that they could spend on other therapies, Mahmood explained.

Response to immunotherapy often cannot be measured effectively at early time points by traditional imaging techniques that measure tumor size, such as CT and MRI scans, or those that measure tumor glucose uptake, such as FDG PET, because these techniques cannot distinguish a nonresponding tumor from a tumor that is responding to immunotherapy but appears to grow in size because it is filled with immune cells and accompanied by increased glucose uptake, Mahmood noted. Tissue biopsies can be unreliable because of tumor heterogeneity and constant changes in the levels of the biomarker proteins measured.

How the Study Was Conducted: Mahmood and colleagues designed a probe that binds to granzyme B--a protein that immune cells release to kill their target--after it is released from the immune cells, so they could directly measure tumor cell killing. The researchers attached the probe to a radioactive atom and used PET scanning to noninvasively image the entire body and see where immune cells are actively releasing tumor-killing granzyme B.

Results:The team tested their probe in tumor-bearing mice before and after treatment with immune checkpoint inhibitors and found that one group of mice had high PET signal, meaning high levels of granzyme B in the tumors, while the other group had low levels of PET signal in the tumors. When the two groups of mice were followed, all mice with high PET signal responded to the therapy and their tumors subsequently regressed, whereas those with low PET signal did not respond to the therapy, and their tumors continued to grow.

"Because PET imaging is quantitative, we could measure the degree of effectiveness and put a number on it," Mahmood added. When they compared the data from monotherapy and combination therapy, they saw a significant increase in tumor granzyme B PET signal in the combination group.

The researchers then collaborated with Keith Flaherty, MD, and Genevieve Boland, MD, PhD, from MGH, and tested their probe on nine human melanoma biopsy samples, six from patients treated with nivolumab (Opdivo) and three from those treated with pembrolizumab (Keytruda). They detected high levels of granzyme B in the samples from responders and much lower levels in the samples from nonresponders.

Author Comment: "The ability to differentiate early in the course of treatment patients who are likely to benefit from immunotherapy from those who will not can greatly improve individual patient care and help accelerate the development of new therapies," Mahmood said.

"In our study, we found a marker that was highly predictive of response to immunotherapy at a very early time after starting treatment, and we were able to design an imaging probe to detect this marker and accurately predict response noninvasively," said Mahmood.

"These findings could have a significant impact on drug development, as different combinations could be imaged at very early time points in patients and the levels of tumor granzyme B used to compare treatments and rank effectiveness," Mahmood said. "Further, therapeutics that achieve high levels of granzyme B release can be advanced faster and those leading to low granzyme B release can be altered or eliminated."
-end-
Limitations: A limitation of the study is that the probe has not yet been tested in the clinic, but the researchers are actively pursuing it, Mahmood noted.

Funding & Disclosures: This study was funded by the National Institutes of Health. Mahmood is the cofounder and consultant at CytoSite BioPharma, a company that is further developing the granzyme B PET imaging probe for clinical translation.

Follow us: Cancer Research Catalyst http://blog.aacr.org; Twitter @AACR; and Facebook http://www.facebook.com/aacr.org

About the American Association for Cancer Research

Founded in 1907, the American Association for Cancer Research (AACR) is the world's first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 37,000 laboratory, translational, and clinical researchers; population scientists; other health care professionals; and patient advocates residing in 108 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis, and treatment of cancer by annually convening more than 30 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 21,900 attendees. In addition, the AACR publishes eight prestigious, peer-reviewed scientific journals and a magazine for cancer survivors, patients, and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration, and scientific oversight of team science and individual investigator grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and other policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit http://www.AACR.org.

American Association for Cancer Research

Related Immune Cells Articles:

Identification of new populations of immune cells in the lungs
In an article published in Nature Communications, the Immunophysiology Laboratory of the GIGA Institute, headed by Prof.
A genomic barcode tracker for immune cells
A new research method to pinpoint the immune cells that recognise cancer could significantly change how we treat the disease.
Scientists reminded immune cells on what side they should be
International group of scientists in the joint study of the laboratory of the Wistar Institute, University of Pittsburgh and I.M.
Dead cells disrupt how immune cells respond to wounds and patrol for infection
Immune cells prioritise the clearance of dead cells overriding their normal migration to sites of injury.
Study gives new perspective on production of blood cells and immune cells
A new study provides a thorough accounting of blood cell production from hematopoietic stem cells.
More Immune Cells News and Immune Cells Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Erasing The Stigma
Many of us either cope with mental illness or know someone who does. But we still have a hard time talking about it. This hour, TED speakers explore ways to push past — and even erase — the stigma. Guests include musician and comedian Jordan Raskopoulos, neuroscientist and psychiatrist Thomas Insel, psychiatrist Dixon Chibanda, anxiety and depression researcher Olivia Remes, and entrepreneur Sangu Delle.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...