{"entity":{"id":"paper-sethna-rna-neoantigen-vaccine-long-lived-t-cells-nature-2025","kind":"paper","name":"RNA neoantigen vaccines prime long-lived CD8+ T cells in pancreatic cancer","aka":[],"tldr":"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.","asOf":"2026-09-24","links":[{"label":"Nature 2025","url":"https://doi.org/10.1038/s41586-024-08508-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39972124/"},{"label":"ClinicalTrials.gov NCT04161755","url":"https://clinicaltrials.gov/study/NCT04161755"},{"label":"ClinicalTrials.gov NCT05968326","url":"https://clinicaltrials.gov/study/NCT05968326"}],"tags":["pancreatic-evidence"],"related":["paper-rojas-mrna-neoantigen-vaccine-pancreatic-nature-2023","immunotherapy-roadmap"],"cancers":["pancreatic","resectable-pdac"],"sections":[],"technologies":["neoantigen-mrna-vaccine","checkpoint-inhibitor"],"targets":[],"drugs":["autogene-cevumeran","atezolizumab","folfirinox"],"companies":["biontech","roche-genentech"],"institutions":["mskcc"],"pathways":[],"terms":["neoantigen","cold-vs-hot"],"trials":["nct05968326"],"people":["vinod-balachandran","ugur-sahin","eileen-oreilly"],"bottlenecks":["b-tme-immunosuppression","b-immunotherapy-response"],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2025,"doi":"10.1038/s41586-024-08508-4","pmid":"39972124","authors":"Sethna Z, Guasp P, Reiche C, et al.","paperType":"translational","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."],"whatItMeans":"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."],"participants":16},"route":"/key-papers/paper-sethna-rna-neoantigen-vaccine-long-lived-t-cells-nature-2025/","neighbours":{"paper":[{"id":"paper-rojas-mrna-neoantigen-vaccine-pancreatic-nature-2023","kind":"paper","name":"Rojas 2023: a personalised mRNA vaccine trained T cells against each patient's pancreatic cancer, and those who responded stayed cancer-free longer","route":"/key-papers/paper-rojas-mrna-neoantigen-vaccine-pancreatic-nature-2023/"}],"roadmap":[{"id":"immunotherapy-roadmap","kind":"roadmap","name":"Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity","route":"/roadmaps/immunotherapy-roadmap/"},{"id":"pancreatic-roadmap","kind":"roadmap","name":"Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question","route":"/roadmaps/pancreatic-roadmap/"}],"cancer":[{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"resectable-pdac","kind":"cancer","name":"Resectable pancreatic ductal adenocarcinoma","route":"/cancers/resectable-pdac/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"neoantigen-mrna-vaccine","kind":"technology","name":"Personalised neoantigen (mRNA) vaccines","route":"/technologies/neoantigen-mrna-vaccine/"}],"drug":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"autogene-cevumeran","kind":"drug","name":"Autogene cevumeran","route":"/drugs/autogene-cevumeran/"},{"id":"folfirinox","kind":"drug","name":"FOLFIRINOX / mFOLFIRINOX","route":"/drugs/folfirinox/"}],"company":[{"id":"biontech","kind":"company","name":"BioNTech","route":"/companies/biontech/"},{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"institution":[{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"}],"term":[{"id":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","route":"/terms/cold-vs-hot/"},{"id":"neoantigen","kind":"term","name":"Neoantigen","route":"/terms/neoantigen/"}],"trial":[{"id":"nct05968326","kind":"trial","name":"A Study of the Efficacy and Safety of Adjuvant Autogene Cevumeran Plus Atezolizumab and mFOLFIRINOX Versus mFOLFIRINOX Alone in Participants With Resected PDAC","route":"/trials/nct05968326/"}],"person":[{"id":"eileen-oreilly","kind":"person","name":"Eileen M. O'Reilly","route":"/people/eileen-oreilly/"},{"id":"ugur-sahin","kind":"person","name":"Uğur Şahin","route":"/people/ugur-sahin/"},{"id":"vinod-balachandran","kind":"person","name":"Vinod P. Balachandran","route":"/people/vinod-balachandran/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}],"journal":[{"id":"nature","kind":"journal","name":"Nature","route":"/journals/nature/"}]}}