A neoantigen vaccine generates antitumour immunity in renal cell carcinoma.
Level 4 - case-series / case-control
Phase I single-arm clinical trial (case series)
PubMed 39910301 · doi:10.1038/s41586-024-08507-5
What was done
A phase I trial (NCT02950766) evaluated a personalized neoantigen-targeting cancer vaccine (PCV), administered with or without adjacent ipilimumab, in 9 patients with fully resected, high-risk clear cell renal cell carcinoma (stage III or IV). Investigators measured safety, recurrence rates, and peripheral as well as autologous tumor-reactive T-cell responses over a median follow-up of 40.2 months after surgery.
What was found
No dose-limiting toxicities were observed. At a median follow-up of 40.2 months after surgery, 0 of the 9 participants had a recurrence of RCC. All 9 patients developed T-cell immune responses against PCV antigens, including responses to driver mutations in VHL, PBRM1, BAP1, KDM5C, and PIK3CA, along with durable expansion of peripheral T-cell clones. T-cell reactivity against autologous tumours was detected in 7 of 9 patients.
Why it matters
This study provides proof-of-concept that personalized neoantigen vaccines can induce targeted immune responses against key cancer driver mutations in renal cell carcinoma, a tumor type with a relatively low mutational burden.
Limits
The study is restricted by a very small sample size (n = 9) and lacks a control group, precluding definitive conclusions about recurrence-free survival benefits. Concomitant use of ipilimumab in a subset of patients also confounds attribution of the observed outcomes.
Cited by
- partial Personalized neoantigen vaccines have achieved cures in patients with treatment-refractory pancreatic cancer and renal cell carcinoma.