Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer

Abstract Pancreatic ductal adenocarcinoma (PDAC) is lethal in 88% of patients 1 , yet harbours mutation-derived T cell neoantigens that are suitable for vaccines 2,3 . Here in a phase I trial of adjuvant autogene cevumeran, an individualized neoantigen vaccine based on uridine mRNA–lipoplex nanoparticles, we synthesized mRNA neoantigen vaccines in real time from surgically resected PDAC tumours. After surgery, we sequentially administered atezolizumab (an anti-PD-L1 immunotherapy), autogene cevumeran (a maximum of 20 neoantigens per patient) and a modified version of a four-drug chemotherapy regimen (mFOLFIRINOX, comprising folinic acid, fluorouracil, irinotecan and oxaliplatin). The end points included…

• DR
  Damon Runyon Cancer Research Foundation
• LF
  Lustgarten Foundation
• PS
  Pershing Square Sohn Cancer Research Alliance
• CF
  Cycle for Survival
• NI
  National Institutes of Health

  Awards: CCSG, P30 CA08748, P30 CA08748, CA08748
• G
  Genentech
• SU
  Stand Up To Cancer
• MA
  Marie-Josée and Henry R. Kravis Center for Molecular Oncology
• NC
  National Cancer Institute

  Awards: P30 CA08748, CA08748, CA224175, CCSG, P30 CA08748
• MR
  Moonshot Research and Development Program
• CM
  Cancer Moonshot