Novel Imaging Test shows promise for identifying kidney cancer patients most likely to benefit from immunotherapy. In a study publish today in the Journal for ImmunoTherapy of Cancer, investigators with the UT Southwestern Medical Center Kidney Cancer Program develop a new test to illuminate kidney cancers that may respond to checkpoint inhibitors.
Immuno therapy drug
The strategy involve transforming an immuno therapy drug, atezolizumab (Tecentriq, Genentech/Roche Group), into a diagnostic tracer. Atezolizumab, which is use to treat lung, breast, and bladder cancer, binds to and disables PD-L1; so a protein that cancer cells display on their surface to shut off approaching killer immune cells.
By labeling atezolizumab with zirconium-89 (Zr89), a radioactive metal generate using a cyclotron; so the investigators were able to visualize atezolizumab using PET (positron emission tomography). As such, a single, very small dose of Zr89-atezolizumab can use to evaluate; so whether tumors deploy PD-L1 to suppress immune cells and whether drugs disabling this pathway may be effective.
In proof-of-principle experiments, a team led by Dr. James Brugarolas, one of the corresponding authors of the study and the Director of the UT Southwestern Kidney Cancer Program, show that Zr89-atezolizumab was able to illuminate kidney tumors with high levels of PD-L1. As part of the study, investigators select tumors from two patients; so one with high PD-L1 and another with low PD-L1, and transplant them into mice.
The substantial regression
The mice were then inject with Zr89-atezolizumab intravenously and evaluate by PET. As predict from the mouse studies, the patient with the high PD-L1 tumor had substantial regression of his metastases when treat with nivolumab (Opdivo, Bristol-Myers Squibb), which targets the PD-L1 pathway.
Dr. Hans Hammers, an immunotherapy expert with the Kidney Cancer Program. Zr89-atezolizumab was filed with the U.S. Food and Drug Administration by the Cyclotron and Radiochemistry Program led by Dr. Xiankai Sun at UT Southwestern, also a corresponding author of the study, and is now proceeding to evaluation in patients in a clinical trial at UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center.
So The clinical trial is made possible through a $600,000 translational award to Dr. Brugarolas’ team by the V Foundation for Cancer Research. Support for the pre clinical studies was provide through a Specialize Program of Research Excellence (SPORE) grant from the National Cancer Institute.
“SBRT has the potential to induce inflammation and activate an immune response, and they are excite to evaluate this therapy further in patients using iPET,” said Dr. Raquibul Hannan, a leader in radiation therapy for kidney cancer and Principal Investigator of the study. The SBRT trial will be fund by the Kidney Cancer Congressionally Direct Medical Research Program.