Personalized Kidney Cancer Vaccines Provide Direction to Immune Therapy

Commentary
Video

Combining renal vaccines with immune therapy may better target tumor cells while limiting harm to healthy tissue, according to David A. Braun, MD, PhD.

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 the advantages personalized tumor vaccines may offer as a treatment for patients with renal cell carcinoma following a presentation of a phase 1 trial (NCT02950766) he gave at the 2025 Kidney Cancer Research Summit.

Braun initially described a shortcoming associated with contemporary immune therapies, which exhibit activity against tumors but may indiscriminately attack healthy tissue. Due to this lack of direction, he explained that many patients may lack on-tumor activity that make immune therapies effective. Additionally, they may experience an onset of adverse effects (AEs) associated with the treatment.

He further suggested that the vaccines assessed in the phase 1 trial are meant to provide direction to existing immune therapies without replacing them, likening the immune therapy to a vehicle and the vaccine to a steering wheel. In this way, this combination may help to bolster efficacy while mitigating AEs.

Transcript

Many of the treatments that we have, particularly the immune therapies, are phenomenal at essentially activating or reinvigorating the immune system, but they don’t tell the immune system where to go. They don’t say, “Attack the tumor cells,” and they don’t say, “Spare or don’t attack the normal parts of the body.” Because of that, while they have been so transformative, we know that there are many patients who don’t benefit because they lack on-tumor activity of the immune system. There’s, unfortunately, many patients who have [adverse] effects [and] toxicities because the immune system is activated and attack other parts of the body.

The question is, how can we flip the balance? How can we direct the immune system in a very specific way? I don’t think it’s [in place] of other treatments, but I think it’s a tool to use with other treatments. Like the car analogy, it’s not that it’s sufficient to have a steering wheel by itself; you still need the car to go. But adding the steering wheel gives it directionality.

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

Recent Videos
Treatment with the dual inhibitor displayed a short half-life and a manageable toxicity profile in patients with clear cell renal cell carcinoma.
The annual Kidney Cancer Research Summit was born from congressional funding for kidney cancer research, according to KidneyCAN president Bryan Lewis.
Improving data collection and biomarker development across institutions may represent areas of expansion in kidney cancer research.
KIM-1 is a biomarker in the blood that may help noninvasively detect kidney cancer, according to Wenxin (Vincent) Xu, MD.
A phase 0 trial is seeking to assess the feasibility of aiding anti-cancer cells with cytokines to restore their function.
Although pembrolizumab addressed a long-standing need in adjuvant kidney cancer treatment, combinations with the agent may further bolster efficacy.
“The trial will be successful, or [we’ll] declare it a success if we see at least 3 of 24 responses overall,” stated Ravi, MD, BChir, MRCP, on the phase 2 LASER trial in RCC.
Success with the 177Lu-PSMA-617 radioligand therapy would be transformative for the clear cell renal cell carcinoma treatment landscape.
Related Content