Personalized Cancer Vaccine Shows Promise in Advanced Kidney Cancer Trial

A groundbreaking study has demonstrated the potential of personalized cancer vaccines in preventing recurrence of advanced kidney cancer, marking a significant milestone in the field of immunotherapy. The small-scale trial, conducted by researchers at the Dana-Farber Cancer Institute, offers new hope for patients with clear-cell renal cell carcinoma, the most common form of kidney cancer.

Impressive Results in Phase 1 Trial

In a phase 1 trial published in Nature on February 5, 2025, researchers reported that nine patients with stage 3 or 4 clear-cell renal cell carcinoma remained cancer-free for over three years after receiving a personalized cancer vaccine following surgical removal of their tumors. This outcome is particularly noteworthy given the high risk of recurrence associated with advanced kidney cancer.

The experimental vaccine was designed to target specific mutant proteins, known as neoantigens, identified from each patient's tumor. Using an algorithm, researchers selected neoantigens most likely to stimulate an immune response. The vaccine was administered on a specific schedule, with patients receiving doses on days 1, 4, 8, 15, and 22 after surgery, followed by boosters at weeks 12 and 20.

Dr. Toni Choueiri, director of Dana-Farber's Lank Center for Genitourinary Oncology, emphasized the significance of these results, stating, "This cancer has a high risk of recurrence, and our findings suggest that personalized vaccines could be a powerful tool in preventing its return."

Immune Response and Safety Profile

The study revealed a remarkable 166-fold increase in cancer-targeting T cells following vaccination. These immune cells persisted throughout the study's duration, indicating a robust and lasting immune response.

In terms of safety, the most common side effects were local reactions at the injection site and flu-like symptoms. One patient in the study died due to mental health complications unrelated to the cancer or treatment. Five patients also received the checkpoint inhibitor antibody Yervoy (ipilimumab) in combination with the vaccine, though the specific outcomes for this subgroup were not detailed in the report.

Implications for Future Research

This trial's success extends the potential of personalized neoantigen vaccines beyond cancers with high mutation burdens, such as melanoma, to those with fewer mutations like kidney cancer. Dr. Patrick Ott, director of Dana-Farber's Center for Cancer Vaccines, noted, "These results support the feasibility of creating a highly immunogenic personalized neoantigen vaccine in a lower mutation burden tumor."

Building on these promising results, a larger randomized phase 2 trial is already underway. This study aims to evaluate a similar personalized vaccine in combination with Merck's Keytruda (pembrolizumab) in approximately 272 patients with renal cell carcinoma.

The pharmaceutical industry is showing increased interest in cancer vaccines, with several collaborations and studies in progress. Merck is partnering with Moderna on an mRNA-based cancer vaccine currently in a phase 3 trial for high-risk melanoma. Additionally, IO Biotech is testing a Keytruda-vaccine combination in squamous cell carcinoma of the head and neck. GSK has also entered the field, recently establishing a research partnership with the University of Oxford to explore neoantigen-based approaches.

As larger trials progress and more data becomes available, personalized cancer vaccines may emerge as a powerful new tool in the fight against various forms of cancer, potentially revolutionizing treatment approaches and improving patient outcomes.