A new technique involving noninvasive PET imaging has been used to accurately predict cancer patients’ responses to immunotherapies.
While immunotherapies have been shown to be highly effective at treating cancer, many patients do not respond to the treatment and only experience unpleasant side effects.
Predicting patients’ probable responses to immunotherapies is problematic, as is determining whether immunotherapy treatment is effective, at least in the early stages of a treatment program.
While CT and MRI scans can be used to determine whether there has been any change in the size of tumors following immunotherapy, the results of those scans can be misleading.
A tumor can increase in size following treatment, but that could be due to continued growth of the tumor or the tumor growing due to increased glucose uptake or because the tumor is filled with immune cells.
Biopsies of the tumor can also produce misleading results due to tumor heterogeneity and the constant changes in biomarker proteins. Consequently, many patients end up wasting time undergoing treatments that are ineffective which can delay the start of other, more beneficial treatments.
Thanks to the work of Umar Mahmood, MD, PhD, professor of radiology at Harvard Medical School, and his team, oncologists could soon be provided with a new tool to determine whether immunotherapies will be effective.
Mahmood and his team developed a probe that measures the level of the protein granzyme B in tumors. Granzyme B is released by immune cells to kill tumor cells. By measuring the levels of granzyme B, Mahmood and his team were able to determine whether immune cells were attacking the tumor.
The probe was attached to a radioactive atom with the team using noninvasive PET imaging to determine the levels of granzyme B in tumors.
The team measured levels in tumor-bearing mice before and after treatment. Mice that had a high PET signal had high levels of granzyme B in the tumors. Those with a low signal had low levels of granzyme B. The team found that tumors regressed following treatment in mice that had a high PET signal, whereas the tumors continued to grow in mice that had a low PET signal.
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.” Mahmood went on to explain, “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.”
By using this noninvasive PET imaging technique, it would be straightforward to check the effectiveness of immunotherapies. Mahmood also pointed out that the technique could be used to help develop new treatments. Any therapy that results in increased granzyme B levels could be advanced faster, whereas those that fail to increase granzyme B levels could be eliminated or altered.
The study was recently published in the Journal Cancer Research.