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 tumor, and result in clinical activity are largely unknown, particularly in patients with lower mutation burden tumors. We conducted a phase I trial testing 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 from surgery, none of the 9 initial participants experienced a recurrence of RCC. No dose-limiting toxicities were observed. All patients generated T cell immune responses against PCV antigens, including RCC driver mutations in <a href="https://www.ncbi.nlm.nih.gov/gene/7428">VHL</a><a href="https://www.ncbi.nlm.nih.gov/gene/7428"></a>, <a href="https://www.ncbi.nlm.nih.gov/gene/55193">PBRM1</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/8314">BAP1</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/8242">KDM5C</a>, and <a href="https://www.ncbi.nlm.nih.gov/gene/5290">PIK3CA</a>. Following vaccination, there was a durable expansion of peripheral T cell clones, and T cell reactivity against autologous tumor was detected in 7 of the 9 patients. Our results demonstrate that neoantigen-targeting PCVs in high-risk RCC are highly immunogenic, capable of targeting key driver mutations, and induce anti-tumor immunity. These observations, in conjunction with the absence of recurrence in all 9 vaccinated patients, highlights the promise of PCV as effective adjuvant therapy in RCC. We are submitting WES data from whole blood samples and tumor FFPE samples, and RNA-Seq data from tumor FFPE samples. We are also submitting RNA-Seq data from purified tumor samples. scRNA-seq data will be submitted for skin samples (vaccine site biopsies at Weeks 0, 4, and 13), tumor samples (including resected metastatic tumor samples for two patients), and normal kidney samples. Bulk TCR-seq data will be submitted for blood samples.

A Personalized Neoantigen Vaccine Generates Anti-Tumor Immunity in    High-Risk Renal Cell Carcinoma

Cancer Vaccines study with RNA-Seq, WXS data on dbGaP (9 participants)

A Personalized Neoantigen Vaccine Generates Anti-Tumor Immunity in High-Risk Renal Cell Carcinoma

Description

Applying For Access

Summary