A neoantigen vaccine generates antitumour immunity in renal cell carcinoma
A neoantigen-targeting personalized cancer vaccine (PCV) administered as adjuvant therapy in high‑risk, fully resected clear cell renal cell carcinoma (RCC) demonstrated potent immunogenicity, elicited T‑cell responses against driver mutations, and was associated with no disease recurrence among nine patients over a median follow‑up of 40 months.
Personalized cancer vaccines (PCVs) can generate circulating immune responses against predicted neoantigens. However, whether such responses can target cancer driver mutations, lead to immune recognition of a patient’s tumour and result in clinical activity are largely unknown. Here we conducted a phase I trial (ClinicalTrials.gov identifier NCT02950766) to test a neoantigen-targeting PCV in patients with high‑risk, fully resected clear cell RCC (stage III or IV) with or without ipilimumab administered adjacent to the vaccine. At a median follow‑up of 40.2 months after surgery, none of the 9 participants enrolled in the study had a recurrence of RCC. No dose‑limiting toxicities were observed. All patients generated T‑cell immune responses against the PCV antigens, including to RCC driver mutations in VHL, PBRM1, BAP1, KDM5C and PIK3CA. Following vaccination, there was a durable expansion of peripheral T‑cell clones. Moreover, T‑cell reactivity against autologous tumours was detected in seven out of nine patients. Our results demonstrate that neoantigen-targeting PCVs in high‑risk RCC are highly immunogenic, capable of targeting key driver mutations and can induce antitumour immunity.
Renal cell carcinoma is a common urologic malignancy with a relatively low mutational burden and limited response to checkpoint inhibitors in the adjuvant setting. Demonstrating that a personalized neoantigen vaccine can safely induce robust, durable T‑cell responses and prevent recurrence in a small cohort of high‑risk patients provides proof‑of‑concept that vaccine‑based adjuvant therapy can bridge the unmet need for durable disease control after surgery. These findings inform future larger, randomized trials and support the integration of neoantigen vaccines into multimodal treatment strategies.
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