# RNA neoantigen vaccines prime long-lived CD8+ T cells in pancreatic cancer

Source: https://onco.cc/key-papers/paper-sethna-rna-neoantigen-vaccine-long-lived-t-cells-nature-2025/  
OnCo record `paper-sethna-rna-neoantigen-vaccine-long-lived-t-cells-nature-2025` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The 2025 follow-up of the personalised mRNA vaccine trial in pancreatic cancer: at three years, patients whose immune systems responded to the vaccine had still mostly not relapsed, and the T cells the vaccine made were predicted to live for years.

## Summary

Sethna, Balachandran and colleagues report the extended 3.2-year median follow-up of the phase 1 trial of surgery, atezolizumab, autogene cevumeran (individualised uridine mRNA-lipoplex neoantigen vaccine) and modified FOLFIRINOX in resected pancreatic ductal adenocarcinoma. Responders with vaccine-induced T cells (8) had prolonged recurrence-free survival (median not reached) compared with non-responders (8; median 13.4 months; P = 0.007). Vaccine-induced CD8-positive T cell clones had an average estimated lifespan of 7.7 years (range 1.5 to roughly 100), about 20 percent with latent multi-decade lifespans; 86 percent of clones per patient persisted at substantial frequency about three years after vaccination. Using PhenoTrack, the clones were shown to be absent from pre-vaccination tissue and to assume a cytotoxic, tissue-resident memory-like state with preserved neoantigen-specific function. Two responders recurred with fewer vaccine-induced T cells, and recurrent tumours were pruned of vaccine-targeted clones.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: pancreatic-evidence
- Journal: Nature
- Year: 2025
- DOI: 10.1038/s41586-024-08508-4
- Authors: Sethna Z, Guasp P, Reiche C, et al.
- Findings: 3.2-year median follow-up; responders (8) median recurrence-free survival not reached versus 13.4 months in non-responders (8), P = 0.007.; Vaccine-induced CD8 clones with an estimated average lifespan of 7.7 years; 86 percent of clones persisted at about three years.; Recurrent tumours in two responders had lost the vaccine-targeted clones.
- What it means: The strongest human evidence that a cancer vaccine can make durable T cells in a tumour with few mutations; the randomised phase 2 IMCODE003 (260 patients, primary completion listed for January 2031) is the test of whether that translates into fewer relapses.
- Caveats: Sixteen patients, half responders; responder status could mark a favourable immune system rather than a vaccine effect.; Manufacturing an individual vaccine within weeks of surgery is a logistical and cost constraint at scale.

## Sources

- Nature 2025: https://doi.org/10.1038/s41586-024-08508-4
- PubMed: https://pubmed.ncbi.nlm.nih.gov/39972124/
- ClinicalTrials.gov NCT04161755: https://clinicaltrials.gov/study/NCT04161755
- ClinicalTrials.gov NCT05968326: https://clinicaltrials.gov/study/NCT05968326

## Connected records

- key papers: [Rojas 2023: a personalised mRNA vaccine trained T cells against each patient's pancreatic cancer, and those who responded stayed cancer-free longer](https://onco.cc/key-papers/paper-rojas-mrna-neoantigen-vaccine-pancreatic-nature-2023/)
- roadmaps: [Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity](https://onco.cc/roadmaps/immunotherapy-roadmap/), [Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question](https://onco.cc/roadmaps/pancreatic-roadmap/)
- cancers: [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Resectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/resectable-pdac/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Personalised neoantigen (mRNA) vaccines](https://onco.cc/technologies/neoantigen-mrna-vaccine/)
- drugs: [Atezolizumab](https://onco.cc/drugs/atezolizumab/), [Autogene cevumeran](https://onco.cc/drugs/autogene-cevumeran/), [FOLFIRINOX / mFOLFIRINOX](https://onco.cc/drugs/folfirinox/)
- companies: [BioNTech](https://onco.cc/companies/biontech/), [Roche / Genentech](https://onco.cc/companies/roche-genentech/)
- institutions: [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/)
- terms: [Hot vs cold tumours](https://onco.cc/terms/cold-vs-hot/), [Neoantigen](https://onco.cc/terms/neoantigen/)
- trials: [A Study of the Efficacy and Safety of Adjuvant Autogene Cevumeran Plus Atezolizumab and mFOLFIRINOX Versus mFOLFIRINOX Alone in Participants With Resected PDAC](https://onco.cc/trials/nct05968326/)
- people: [Eileen M. O'Reilly](https://onco.cc/people/eileen-oreilly/), [Uğur Şahin](https://onco.cc/people/ugur-sahin/), [Vinod P. Balachandran](https://onco.cc/people/vinod-balachandran/)
- bottlenecks: [Cold tumours and the immunosuppressive microenvironment](https://onco.cc/bottlenecks/b-tme-immunosuppression/), [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/)
- journals: [Nature](https://onco.cc/journals/nature/)

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