Impact of personalized peptide neoantigen vaccines on immunologic responses in patients with pancreatic cancer.

Abstract

e16351 Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer that often resists conventional therapies. One of the most promising alternative treatments is personalized neoantigen vaccines that target specific mutations in each patient’s tumor. These vaccines aim to activate the immune system to fight cancer cells. However, how this type of vaccine affects immune cells across different vaccination phases is poorly understood. Methods: Here we report the safety and dynamic immunological responses of peptide-based vaccines after chemotherapy in patients with resected PDAC in a single-center open-label phase 1b trial (registered at ClinicalTrials.gov [NCT03558945]). The primary endpoint was safety, assessed by the incidence of adverse events in all vaccinated patients. The key secondary endpoints included prognosis assessed by recurrence-free survival and overall survival rate. Results: We observed only 3 grade ≥3 adverse events in 2 patients (12.5%) and no grade ≥4 events. Vaccinated patients achieved favorable survival outcomes, with a 3-year recurrence-free survival rate of 56% and a 3-year overall survival rate of 74%. Using single-cell sequencing, we revealed the dynamics of vaccine-induced immune responses, with CD8+ cytotoxic T cells expanding at the priming phase and CD4+ T cells at the boosting phase. The CD8+ cytotoxic T cells had a higher proportion (average, 38.4%) of persistent expansion than the CD4+ T cells (average, 3.7%), with a range of 2.8~21.8 months duration. We also discovered a helper B-cell subtype that interacted with T cells and was associated with prognosis, suggesting a role for B-cell epitopes in vaccine effectiveness. Conclusions: These results provide valuable insights for optimizing peptide-based neoantigen vaccine design, regimen, and evaluation strategies. Clinical trial information: NCT03558945 .