Giving the Immune System a “Steering Wheel” in Kidney Cancer Management

In a visit to Yale Cancer Center in New Haven, Connecticut, CancerNetwork® spoke with David A. Braun, MD, PhD, about his research on a novel neoantigen vaccine as a treatment for patients with kidney cancer, specifically those with renal cell carcinoma (RCC). He spoke in the context of a phase 1 trial (NCT02950766) demonstrating the potential immunogenic activity of a personalized cancer vaccine among 9 patients with high-risk clear cell RCC.

According to Braun, assistant professor at Yale School of Medicine and principal investigator in the Center of Molecular and Cellular Oncology within the Yale Cancer Center, a cancer vaccine aims to add a “steering wheel” to the immune system, directing it to attack malignant cells while sparing healthy parts of the body. He emphasized exhibiting caution when interpreting the results of the phase 1 trial, which require validation at a larger level.

Transcript:

The basic idea behind a personalized cancer vaccine is to add a steering wheel to the immune system. We know that, in general, immune therapies have been transformative for many patients with kidney cancer. But the tools we use today are pretty crude. They essentially take the brake off the immune system, and the hope is that [the] unleashed immune system will go and attack kidney cancer cells but not attack normal parts of the body. For many patients, that’s true. Unfortunately, we know that in many cases, that’s not the situation. Many patients do not receive benefit from current therapies, and many patients experience [adverse] effects.

The idea behind a personalized cancer vaccine is, “Can we find something that’s unique to each individual’s tumor that essentially adds a sort of GPS [Global Positioning System]? Can we steer the immune system in that direction to specifically attack those cancer cells?” This is an early effort. This is a first-in-disease effort—only 9 patients—so we have to be cautious about the interpretation of results. But what we saw was encouraging; it was feasible to do this, safe to do this, and the early signs that we wanted to see that would generate an immune response were successful. Clinically, while the early results were encouraging, we have to validate this at a much larger level.

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