A personalized vaccine for kidney cancer

Abstract

Despite the emergence of immune-based therapies, patients who undergo nephrectomy for clear cell renal cell carcinoma (ccRCC) remain at high risk of cancer recurrence, highlighting an unmet clinical need to improve outcomes for these patients. Personalized cancer vaccines (PCVs) aimed at neoantigens derived from tumour-specific mutations have demonstrated benefits in patients with tumours having high mutational burdens, such as melanoma. However, the implementation of PCVs for tumours with low mutational burdens has proven challenging. Findings from a single-arm, phase 1 clinical trial now demonstrate the feasibility of a PCV in patients at high risk of kidney cancer recurrence after surgical removal.

To generate the PCV, David Braun and colleagues synthesized a median of 15 neoantigen-containing peptides for each of nine patients. These peptides were allocated to one of four peptide pools, which were subsequently administered to the patients. The immunotherapy drug ipilimumab was also administered to five of the nine patients. “Prior work from the laboratory of Catherine Wu had shown that neoantigen-targeting personalized cancer vaccines could effectively steer the immune system to recognize tumour-specific targets in melanoma and glioblastoma multiforme. We therefore investigated whether a personalized cancer vaccine could lead to effective anti-tumour immunity in high-risk ccRCC,” says Braun. “We found that, despite kidney cancer having a low mutation burden, the PCV was feasible to manufacture for all patients. It was safe and led to durable, ex vivo immune responses against neoantigens that lasted months or even years after vaccination was complete.”