Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer

🤖 Plain-English Summary

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 . 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.

🔑 Key Findings

• 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 vaccine-induced neoantigen-specific T cells by high-threshold assays, 18-month recurrence-free survival and oncologic feasibility.

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