# Rojas 2023: a personalised mRNA vaccine trained T cells against each patient's pancreatic cancer, and those who responded stayed cancer-free longer

Source: https://onco.cc/key-papers/paper-rojas-mrna-neoantigen-vaccine-pancreatic-nature-2023/  
OnCo record `paper-rojas-mrna-neoantigen-vaccine-pancreatic-nature-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: Nature
- Year: 2023
- DOI: 10.1038/s41586-023-06063-y
- Authors: Rojas LA, Sethna Z, Soares KC, et al.
- Findings: 16 patients with resected pancreatic cancer; atezolizumab, then individualised mRNA neoantigen vaccine (up to 20 neoantigens), then mFOLFIRINOX.; Vaccine manufactured and delivered within about 9 weeks of surgery in most patients.; High-magnitude neoantigen-specific T-cell responses in 8 of 16 (50%).; Median recurrence-free survival not reached in responders vs 13.4 months in non-responders; hazard ratio 0.08.; Responding T-cell clones were de novo and persisted for up to several years in the 2025 follow-up.
- What it means: 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.
- Caveats: Tiny, non-randomised study; the association between immune response and recurrence could reflect confounding.; Half the patients did not mount a response, for reasons that are only partly understood (for example, splenectomy).; Manufacturing an individual vaccine within weeks of surgery is expensive and logistically complex.; Clinical benefit awaits the randomised IMCODE003 result.

## Sources

- PubMed search: https://pubmed.ncbi.nlm.nih.gov/?term=Personalized%20RNA%20neoantigen%20vaccines%20stimulate%20T%20cells%20in%20pancreatic%20cancer%20Rojas%20Nature%202023
- ClinicalTrials.gov NCT04161755: https://clinicaltrials.gov/study/NCT04161755

## Connected records

- pairings: [Personalised neoantigen vaccine + PD-1 blockade](https://onco.cc/pairings/vaccine-plus-pd1/)
- key papers: [RNA neoantigen vaccines prime long-lived CD8+ T cells in pancreatic cancer](https://onco.cc/key-papers/paper-sethna-rna-neoantigen-vaccine-long-lived-t-cells-nature-2025/)
- cancers: [Melanoma](https://onco.cc/cancers/melanoma/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Resectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/resectable-pdac/)
- technologies: [Personalised neoantigen (mRNA) vaccines](https://onco.cc/technologies/neoantigen-mrna-vaccine/)
- targets: [PD-1](https://onco.cc/targets/pd1/)
- drugs: [Atezolizumab](https://onco.cc/drugs/atezolizumab/), [Autogene cevumeran](https://onco.cc/drugs/autogene-cevumeran/), [Intismeran autogene](https://onco.cc/drugs/intismeran-autogene/)
- 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: [Neoantigen](https://onco.cc/terms/neoantigen/), [Tumour mutational burden (TMB)](https://onco.cc/terms/tmb/)
- trials: [INTerpath-001 (V940-001)](https://onco.cc/trials/interpath-001/)
- bottlenecks: [Cold tumours and the immunosuppressive microenvironment](https://onco.cc/bottlenecks/b-tme-immunosuppression/), [Manufacturing cost and time for living and radioactive medicines](https://onco.cc/bottlenecks/b-manufacturing-cell-therapy/), [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/)
- journals: [Nature](https://onco.cc/journals/nature/)
- roadmaps: [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/)
- people: [Uğur Şahin](https://onco.cc/people/ugur-sahin/), [Vinod P. Balachandran](https://onco.cc/people/vinod-balachandran/)

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