A group of researchers from the Athinoula A. Martinos Center for Biomedical Imaging Massachusetts General Hospital (MA, USA) have uncovered a way of distinguishing tumors that respond to immune checkpoint inhibitors early in the course of treatment and those that do not. The findings were published recently in Cancer Research.
Although immunotherapy has become one of the most exciting developments in cancer treatment over the last few years, only a minority of patients respond. Therefore, there is an increasing need for reliable response biomarkers to identify those patients who do respond.
In this novel study, a team of scientists report preclinical proof of concept for the use of granzyme B as an early biomarker for tumors responding to immunotherapy.
In order to determine which tumors respond to immunotherapy the researchers designed a probe that binds to granzyme B – a downstream effector of tumoral cytotoxic T cells – attached to a radioactive atom. PET scanning enabled the researchers to pinpoint which cells were releasing granzyme B.
The researchers tested their method in immunotherapy-treated mice which were imaged prior to therapy-induced tumor volume reduction. They demonstrated excellent predictive ability in distinguishing treated responders from non-responders.
Lead author Umar Mahmood (Massachusetts General Hospital) commented: “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.”
The team also assessed the clinical value of the biomarker by analyzing biopsy specimens from melanoma patients on checkpoint inhibitor therapy. Again, a marked difference in granzyme B expression was observed between responders and non-responders.
“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,” explained Mahmood.
Overall, the results suggest that granzyme B PET imaging could serve as a quantative biomarker for effacious responses to immuno-oncology therapies. The team are now actively looking to test their early tumor biomarker in the clinic.
Mahmood concluded: “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. 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.”