Personalized Renal Vaccine Emerges as Encouraging Option in Phase 1 Study

In a conversation with CancerNetwork®, David A. Braun, MD, PhD, assistant professor at Yale School of Medicine and principal investigator in the Center of Molecular and Cellular Oncology within the Yale Cancer Center, discussed what findings from a phase 1 trial (NCT02950766) show about the role personalized vaccines may play as a treatment for patients with renal cell carcinoma following a presentation he gave at the 2025 Kidney Cancer Research Summit.

Braun began by highlighting fundamental questions regarding the use of the vaccine in this patient population, including those regarding its feasibility, safety, and potential efficacy. Furthermore, he highlighted the relative safety of the vaccine, suggesting that adverse effects tended to be low-grade and transient, as well as its durable immunity, which resulted in long-term responses.

Notably, of 9 patients treated in the proof-of-concept study, none had experienced any signs of recurrence, according to Braun. However, noting that 9 patients will not be enough to draw any definitive conclusions regarding the efficacy of the vaccine, he expressed that larger studies investigating the modality may help answer whether it will have a positive impact on patients.

Transcript:

This is the first proof of concept of this idea of a personalized cancer vaccine targeting neoantigens in kidney cancer, and we had some fundamental questions. Was it actually feasible? Kidney cancer doesn’t have a lot of mutations or neoantigens. It’s different from melanoma. Could we actually make this? The answer was yes. Was it safe? The answer was yes there [as well]. The [adverse] effects tended to be low-grade, manageable, and transient. Is it actually doing what we thought it should do, which is activate and steer the immune system? Are we getting immune responses? The answer to that was yes as well.

Next, were those responses transient or short-lived? Or is it really creating durable immunity, and are those immune cells now capable of recognizing and attacking the tumor? And the answer to that was yes as well. Finally, is there at least some signal that it might have clinical activity that might help our patients, which is, of course, the ultimate goal? Now this was a small space: only 9 patients. It was a proof-of-concept, first-in-disease [study]. [It is] hard to draw many conclusions from 9 patients.

Encouragingly, those 9 patients had very high-risk disease and none of those patients had their kidney cancer come back during the study. When we put this all together, this really supports the idea that this should be investigated further. We’re not there yet, where this is still far from a standard treatment, but this is now being investigated in much larger-scale studies that will answer the question, “Is this really having a positive impact for our patients?”

Reference

Braun DA, Moranzoni G, Chea V, et al. A neoantigen vaccine generates antitumour immunity in renal cell carcinoma. Nature. 2025;638:474-482. doi:10.1038/s41586-024-08507-5