Benefits of an immunogenic personalized neoantigen nanovaccine in patients with high-risk gastric/gastroesophageal junction cancer

Personalized neoantigen vaccines have shown strong immunogenicity in clinical trial, but still face various challenges in facilitating an efficient antitumour immune response. Here we prepared a personalized neoantigen nanovaccine (PNVAC) platform for adjuvant cancer immunotherapy. PNVAC triggered superior protective efficacy against tumor recurrence and promoted longer survival than free neoantigens, especially when combined with anti-PD-1 treatment in a murine tumor model. A phase I clinical trial (ChiCTR1800017319) was initiated to study the safety, immunogenicity, and prophylactic effect of PNVAC on preventing tumor recurrence in patients with high-risk gastric/gastroesophageal junction cancer after adjuvant chemotherapy post-surgical resection. The 1- and 2-year disease-free survival rates were significantly higher than historical control. PNVAC induced both CD4+ and CD8+ T cell responses as well as antigen-experienced memory T cell phenotype. Furthermore, the immune response was persistent and remained evident one year after the vaccination. Our work provides a safe and feasible strategy for development of neoantigen vaccines to delay gastric cancer recurrence after surgery.