Personalized Kidney Cancer Vaccines Provide Direction to Immune Therapy

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 makes 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 are, unfortunately, many patients who have [adverse] effects [and] toxicities because the immune system is activated and attacks 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