Faculty, Staff and Student Publications
Publication Date
3-1-2025
Journal
Nature
Abstract
Personalized cancer vaccines (PCVs) can generate circulating immune responses against predicted neoantigens1-6. 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. These questions are of particular interest for patients who have tumours with a low mutational burden. 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 renal cell carcinoma (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. These observations, in conjunction with the absence of recurrence in all nine vaccinated patients, highlights the promise of PCVs as effective adjuvant therapy in RCC.
Keywords
Humans, Carcinoma, Renal Cell, Kidney Neoplasms, Cancer Vaccines, Antigens, Neoplasm, Male, Female, Middle Aged, Aged, Mutation, T-Lymphocytes, Ipilimumab, Class I Phosphatidylinositol 3-Kinases, Precision Medicine, Nuclear Proteins, Adult, Von Hippel-Lindau Tumor Suppressor Protein, Transcription Factors, DNA-Binding Proteins, Tumor Suppressor Proteins, Ubiquitin Thiolesterase
DOI
10.1038/s41586-024-08507-5
PMID
39910301
PMCID
PMC11903305
PubMedCentral® Posted Date
2-5-2025
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons