The Next Step for Immunotherapy

Published in Radiology Update - 2021

After years of work identifying imaging targets and developing imaging agents and techniques in the lab, Sridhar Nimmagadda is seeing his research on imaging the PD-L1 protein in cancers progress to the next step, with the launch of a clinical trial.

Trained as a chemist, Nimmagadda originally started off with an interest in tumor biology. PD-L1 is a protein commonly found in tumors, and there are several existing therapy treatments targeting PD-L1 and its receptor, PD-1. To enrich responses, patients for those therapies are often selected based on PD-L1 expression. When effective, for the few who responded to it, PD-1/PD-L1 targeted immunotherapy is a treatment that changes patients’ lives.

Unfortunately, the majority of patients do not experience a positive response. Concerned by this low rate of effectiveness, Nimmagadda wanted to develop a tool or technique to better optimize these treatments.

PD-L1 detection poses several challenges. Currently, immunohistochemistry is used for detection. “PD-L1 levels are very heterogenous in nature, even within a single tumor and different tumors within a patient, which has relevance to the patient’s response to that therapy. PD-L1 expression can also change rapidly during therapy,” he explains. “Changes during therapy are even more difficult to assess, as biopsies can be difficult to obtain during therapy and based on the type of cancer, so I was interested in finding a noninvasive imaging technique through positron emission tomography.”

Over the course of four years, his lab members, including Dhiraj Kumar, worked closely with colleagues Robert Dannals and Daniel Holt, from the Positron Emissions Tomography Center. They ultimately developed a compound to better image PD-L1 protein levels comprehensively and continually throughout a patient’s therapeutic journey.

The use of a specific radiotracer to serve as a biomarker in monitoring anti-tumor immune response to immunotherapy was given a go-ahead by the FDA to test in a clinical trial that is now enrolling nonsmall cell cancer patients. This clinical team is headed by Lilja Solnes and also includes Steve Rowe, Martin Pomper, Patrick Forde, Rehab Abdallah and many others in the Division of Nuclear Medicine and Molecular Imaging. “We have a dedicated and collegial team that made this happen at Hopkins,” says Nimmagadda.

Meanwhile, Nimmagadda continues his work with oncology and immunoimaging, applying different questions for different types of cancers. “One of the many advantages of this new imaging agent is that we can evaluate any type of immunotherapy that modulates PD-L1 levels in the tumors. Many immune system targeted therapeutics that are approved or in development modulate PD-L1 levels in the tumors, so this imaging agent could find broad applicability in cancer treatment,” he says.

“We eagerly await the data from the clinical trial in order to begin work on guiding and optimizing PD-1/PD-L1 targeted therapies and to take the next steps,” he says. “I remain very much invested in making this a success for the patients.”