Promising Cancer Vaccine Boosts Hope for Stage III and IV Kidney Cancer

Today, Dana-Farber Cancer Institute announced that all 9 patients in a clinical trial (NCT02950766) being treated for stage III or IV clear cell renal cell carcinoma showed significant anticancer immune response after initiation of a personalized cancer vaccine.¹

The findings from the phase 1 trial are published in Nature.²

The trial aimed to determine the safety and efficacy of a neoantigen-based personalized cancer vaccine. | Image credit: radekcho - stock.adobe.com

“This study was the result of a close partnership between our NeoVax team, our colleagues at the Broad Institute of MIT and Harvard, and our colleagues at the Lank Center for Genitourinary Cancer at Dana-Farber,” co–senior author Catherine Wu, MD, chief of the Division of Stem Cell Transplantation and Cellular Therapies at Dana-Farber and an institute member at Broad, who developed the NeoVax vaccine technology used to create the personalized cancer vaccines for this trial, said in a statement.¹ “We are thrilled to report these results.”

The trial aimed to determine the safety and efficacy of a neoantigen-based personalized cancer vaccine.² Following surgical removal of the tumor, each patient received a vaccine tailored to their specific cancer mutations. Five of the 9 participants also received ipilimumab, an immune checkpoint inhibitor, alongside the vaccine.

To develop the vaccine, researchers extracted tumor samples and used predictive algorithms to identify neoantigens—unique cancer-specific protein fragments not present in normal cells. These neoantigens were selected based on their potential to trigger an immune response. The vaccine was then manufactured and administered in an initial series of doses, followed by 2 booster shots.

Renal cell carcinoma is a common cancer characterized by a relatively low mutational burden and defined cancer driver mutations. While immune-based therapies, including both cytokine-based and immune checkpoint inhibitors, have shown antitumor activity in renal cell carcinoma, the disease presents challenges due to its lower mutational burden compared with other cancers like melanoma or lung cancer.

Within 3 weeks of vaccination, there was a significant increase in the number of vaccine-induced T-cells, which expanded by an average of 166-fold.¹ These T-cells remained at elevated levels for up to 3 years, demonstrating long-term persistence. In vitro studies further confirmed that the vaccine-induced T-cells were able to specifically target and attack the patients' tumor cells.

Importantly, no severe adverse events were reported during the trial, with patients only experiencing mild local reactions at the injection site or flu-like symptoms. These findings suggest that the personalized vaccine approach can effectively stimulate a durable immune response, offering hope for improving recurrence prevention for patients with kidney cancer.

These findings are particularly significant given the high recurrence rate of stage III and IV kidney cancer. Current standard treatments include surgery and immunotherapy with pembrolizumab, which reduces recurrence risk but is not effective for all patients. The study demonstrates that a personalized vaccine approach can generate a durable immune response in kidney cancer, a disease with fewer genetic mutations than melanoma, where similar vaccines have shown success.

While these early results are promising, larger clinical trials are needed to confirm the vaccine’s long-term efficacy. An ongoing international randomized trial (NCT06307431) is now evaluating a similar personalized cancer vaccine in combination with pembrolizumab.

“This approach is truly distinct from vaccine attempts in kidney cancer,” David A. Braun, MD, PhD, formerly of Dana-Farber and Harvard Medical School, and now a medical oncologist and physician-scientist at Yale Cancer Center and Yale School of Medicine, in the statement.¹ “We pick targets that are unique to the cancer and different from any normal part of the body, so the immune system can be effectively ‘steered’ towards the cancer in a very specific way. We learned which specific targets in the cancer are most susceptible to immune attack and demonstrated that this approach can generate long-lasting immune responses, directing the immune system to recognize cancer. We believe this work can form a foundation for the development of neoantigen vaccines in kidney cancer.”

References

1. Cancer vaccine shows promise for patients with stage III and IV kidney cancer. News release. Dana-Farber Cancer Institute. February 5, 2025. Accessed February 5, 2025. https://www.dana-farber.org/newsroom/news-releases/2025/cancer-vaccine-shows-promise-for-patients-with-stage-iii-and-iv-kidney-cancer

2. Braun DA, Moranzoni G, Chea V, et al. A neoantigen vaccine generates antitumour immunity in renal cell carcinoma. Nature. Published online February 5, 2025. doi:10.1038/s41586-024-08507-5