Personalized Vaccines Elicit Anti-Cancer Immune Responses in Kidney Cancer

All 9 patients in a phase 1 trial testing a neoantigen-targeting personalized cancer vaccine in renal cell carcinoma had no recurrence at data cutoff.

In a phase 1 trial (NCT02950766), neoantigen-targeting personalized cancer vaccines (PCV) with or without ipilimumab (Yervoy) elicited anti-cancer immune responses in a small cohort of patients with fully resected clear cell renal cell carcinoma (RCC), according to findings published in Nature.¹

Data revealed that the PCVs were immunogenic in all 9 patients enrolled and treated on trial. Furthermore, there were no RCC recurrences observed with a median follow-up of 40.2 months after surgery. Additionally, at a median follow-up of 34.7 months following vaccine administration, the median disease-free survival (DFS) was not reached.

Safety data revealed that the most common adverse events were low-grade injection site reactions in 9 patients and transient flu-like symptoms in 8, with no patients experiencing a grade 3 or higher dose-limiting toxicity (DLT). Two patients experienced white blood cell count decreases, with single instances of fatigue, malaise, alanine aminotransferase increases, neutrophil count decreases, and dry skin. A single patient died from mental health–related complications not associated with treatment or RCC.

“This approach is truly distinct from vaccine attempts in kidney cancer,” lead study author David A. Braun, MD, PhD, medical oncologist and physician-scientist at Yale Cancer Center and Yale School of Medicine, said in a news release.² “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.”

Between March 2019 and September 2021, the phase 1 trial enrolled patients with presumed high-risk RCC to receive either a neoantigen-targeting PCV plus 2.5 mg of subcutaneous ipilimumab at the site of vaccination (n = 5) or the vaccine alone (n = 4). A third cohort treated with a PCV and 5 mg of subcutaneous ipilimumab at the site of vaccination with ongoing follow-up was not included in the results.

A median of 15 peptides containing neoantigens were synthesized, were allocated to 1 of 4 peptide pools, and were administered to patients. All patients were vaccinated with at least 1 frameshift insertion and deletion-resultant peptide, with 7 successfully vaccinated with cancer driver mutation–derived neoantigen-containing peptides.

Patients enrolled on study had a median age of 65.5 years (range, 50.4-75.7) and were predominantly male (78%); the majority had an ECOG performance status score of 0 (78%). All patients had clear cell tumor histology, 7 (78%) had stage III disease, 8 (89%) had International Society of Urological Pathology grade 3 disease, and 7 (78%) patients had primary tumors of 10 cm or smaller.

The primary study end points were safety and tolerability of PCV with ipilimumab, and the maximum tolerated dose of ipilimumab. Secondary end points included neoantigen-specific cellular immune responses after vaccination, and 2-year recurrence-free survival after surgery.

“We observed a rapid, substantial, and durable expansion of new T cell clones related to the vaccine,” senior study author Patrick Ott, MD, PhD, director of the Center for Cancer Vaccines at Dana-Farber Cancer Institute, said in the news release.² “These results support the feasibility of creating a highly immunogenic personalized neoantigen vaccine in a lower mutation burden tumor and are encouraging, though larger scale studies will be required to fully understand the clinical efficacy of this approach.”

References

1. Braun DA, Moranzoni G, Chea V, et al. A neoantigen vaccine generates antitumour immunity in renal cell carcinoma. Nature. Published February 5, 2025. doi:10.1038/s41586-024-08507-5
2. Cancer vaccine shows promise for patients with stage III and IV kidney cancer. News release. Dana-Farber Cancer Institute. February 5, 2025. Accessed February 6, 2025. https://tinyurl.com/yj6jym5s