![]() Surgery is the only curative treatment for PDAC. With an increasing incidence 6, and a survival rate of 12% 1 that has remained largely stagnant for nearly 60 years 1, PDAC is projected to cause even greater global cancer deaths by 2025 (refs. PDAC is the third leading cause of cancer death in the United States 4 and the seventh worldwide 5. Thus, adjuvant atezolizumab, autogene cevumeran and mFOLFIRINOX induces substantial T cell activity that may correlate with delayed PDAC recurrence. Differences in the immune fitness of the patients did not confound this correlation, as responders and non-responders mounted equivalent immunity to a concurrent unrelated mRNA vaccine against SARS-CoV-2. At 18-month median follow-up, patients with vaccine-expanded T cells (responders) had a longer median recurrence-free survival (not reached) compared with patients without vaccine-expanded T cells (non-responders 13.4 months, P = 0.003). ![]() Using a new mathematical strategy to track T cell clones (CloneTrack) and functional assays, we found that vaccine-expanded T cells comprised up to 10% of all blood T cells, re-expanded with a vaccine booster and included long-lived polyfunctional neoantigen-specific effector CD8 + T cells. Autogene cevumeran was administered within 3 days of benchmarked times, was tolerable and induced de novo high-magnitude neoantigen-specific T cells in 8 out of 16 patients, with half targeting more than one vaccine neoantigen. We treated 16 patients with atezolizumab and autogene cevumeran, then 15 patients with mFOLFIRINOX. The end points included vaccine-induced neoantigen-specific T cells by high-threshold assays, 18-month recurrence-free survival and oncologic feasibility. 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). 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. 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. ![]() Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer
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