Research Update: New Kidney Cancer Treatment Method, Trial Ongoing
Dr. Toni Choueiri and Dr. Rizwan Romee received a KCA research award in 2021 for their project “Adoptive cytokine-induced memory-like natural killer cell therapy alone or in combination with avelumab for immunotherapy-refractory advanced renal cell carcinoma.” This technique could represent a new type of immunotherapy treatment Choueiri, Romee, and Dr. Vincent Xu, shared an update on their research, which has led to a clinical trial that is currently enrolling participants. They also published some of their results recently. Choueiri, Romee, and Xu are based at the Dana-Farber Cancer Center in Boston, Massachusetts.
What have been some of your key research findings since you received a KCA grant in 2021?
Our grant had two aims. In Aim 1, we are conducting an ongoing trial of cytokine-induced memory-like natural killer (NK) cell therapy (NCT06318871), which is enrolling patients with kidney cancer and urothelial cancer. This trial involves collecting a patient’s own natural killer cells from the blood, and then treating them in the lab and infusing them back to the patient after lymphodepleting chemotherapy, followed by low dose IL-2. We have treated several kidney cancer patients on this trial so far and enrollment is ongoing. We hope that this trial will teach us about how this treatment works in patients and provide information that will support future studies.
In Aim 2, we are studying how natural killer cells function in kidney cancer patients. We have identified that as kidney cancer grows, it causes disruption in the ability of natural killer cells to fight cancer. Some of these results were recently published in a peer-reviewed journal: Progressive natural killer cell dysfunction in advanced-stage clear-cell renal cell carcinoma and association with clinical outcomes. ESMO Open. 2025 Feb;10(2):104105.
We are investigating potential ways to restore natural killer cell function as a cancer treatment, including cytokine stimulation (such as in the Aim 1 trial) and other strategies such as adding a chimeric antigen receptor (CAR NK), and arming the cells with secreted cytokines.
Have these findings supported your initial hypotheses?
Our initial findings suggest that cytokine-induced memory-like natural killer cells do have the ability to attack kidney cancer. However, we hope to enhance this activity further with ongoing experiments, which we anticipate will lead to the next generation of NK cell trials.
What are the next steps for this work?
We have developed a new NK CAR cell therapy in the lab based on this ongoing work. We are currently validating this new cell therapy and hope to bring it into a clinical trial within the next year.
What are the potential impacts of your work for patients?
Natural killer cell therapy could represent a new type of immunotherapy for kidney cancer. If this is successful, we hope it could add a new tool for kidney cancer oncologists and potentially be effective in treating kidney cancers that are resistant to existing types of immunotherapy such as immune checkpoint inhibitors.
What continues to motivate you?
Dr. Rizwan Romee: I am honored to be at the forefront of cutting-edge research, yet humbled by the reality that we have yet to make significant progress in curing the majority of patients with advanced cancer.
Dr. Toni Choueiri: At DFCI, folks from multiple disciplines and backgrounds collaborate together on the science to benefit patients. This is a unique model that ends up driving innovation in cancer.