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Individualised mRNA vaccines encoding up to 20 of each patient's tumour mutations generated strong T-cell responses in half of pancreatic cancer patients after surgery, and those responders had far fewer relapses.
In this phase 1 study at Memorial Sloan Kettering, 16 patients with resected pancreatic ductal adenocarcinoma received atezolizumab followed by autogene cevumeran, an individualised uridine mRNA-lipoplex vaccine encoding up to 20 predicted neoantigens manufactured within about nine weeks of surgery, and then modified FOLFIRINOX chemotherapy. The vaccine expanded high-magnitude neoantigen-specific T cells in 8 of 16 patients. At a median follow-up of 18 months, responders had not reached median recurrence-free survival whereas non-responders had a median of 13.4 months (hazard ratio 0.08). Vaccine-induced T-cell clones were shown to be newly generated and, in a 2025 follow-up, persisted for years with continued separation of recurrence curves. A randomised phase 2 trial (IMCODE003) in the same setting is under way.
Pancreatic cancer was thought to be immunologically inert because of its low mutation burden; this study showed that with the right vaccine platform its few neoantigens can still be targeted. It is the strongest human evidence so far that personalised cancer vaccines can generate durable, tumour-specific immunity, and it justifies the randomised trials now running in pancreatic cancer and melanoma. Benefit is not yet proven, because responders may simply have had more immunogenic tumours.
Shares Autogene cevumeran, Intismeran autogene, BioNTech, Neoantigen.
Shares Vinod P. Balachandran, Autogene cevumeran, BioNTech, Personalised neoantigen (mRNA) vaccines.
Shares Autogene cevumeran, Intismeran autogene, BioNTech, Neoantigen.
Shares Uğur Şahin, Autogene cevumeran, BioNTech, Neoantigen.
Shares RNA neoantigen vaccines prime long-lived CD8+ T cells in pancreatic cancer, Autogene cevumeran, BioNTech, Personalised neoantigen (mRNA) vaccines.
Shares Vinod P. Balachandran, Neoantigen, Nature, Tumour mutational burden (TMB).
Shares INTerpath-001 (V940-001), Intismeran autogene, Neoantigen, Tumour mutational burden (TMB).
Shares INTerpath-001 (V940-001), BioNTech, Neoantigen, Personalised neoantigen (mRNA) vaccines.