{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:56:17Z","timestamp":1782280577155,"version":"3.54.5"},"posted":{"date-parts":[[2025,5,19]]},"group-title":"Cancer Biology","reference-count":44,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"For a better World Foundation","award":["FABW-001"],"award-info":[{"award-number":["FABW-001"]}]},{"name":"NIH\/NCI","award":["1R21CA286198"],"award-info":[{"award-number":["1R21CA286198"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Immunotherapy shows limited success in pancreatic cancer, largely due to a low mutational burden and immunosuppressive microenvironment. Here we hypothesized that pre-existing antiviral immunity can be redirected to control pancreatic tumors. Cytomegalovirus (CMV, a \u03b2-herpesvirus) was chosen, as the majority of the population is infected and it induces an extremely large\/broad memory T cell response. Mice latently infected with murine CMV (MCMV) were orthotopically implanted with pancreatic cancer cells and treated with systemic injections of MCMV T-cell epitopes. The therapy promoted preferential accumulation of MCMV-specific T cells within pancreatic tumors, delaying tumor growth and increasing survival. Immunophenotyping and scRNAseq analyses showed these T cells were highly activated and cytotoxic, leading to increased tumor necrosis and caspase-3 activation. Finally, therapy was enhanced when combined with subtherapeutic doses of gemcitabine chemotherapy. Together, these results show that CMV-specific T cells can be repurposed to combat pancreatic cancer.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Significance<\/jats:title>\n                  <jats:p>Our studies reveal that CMV-specific viral memory T cells can be re-directed to control a solid tumor normally refractory to immunotherapy via a simple, intravenous injection of T cell peptide epitopes. This mutation agnostic approach has significant potential for the development of \u201coff-the-shelf\u201d therapeutics by stimulating pre-existing antiviral memory and it is widely applicable due to the high prevalence of CMV.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.05.15.654308","type":"posted-content","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T16:35:15Z","timestamp":1747672515000},"source":"Crossref","is-referenced-by-count":0,"title":["Redirecting cytomegalovirus immunity against pancreas cancer for immunotherapy"],"prefix":"10.64898","author":[{"given":"R","family":"Marrocco","sequence":"first","affiliation":[{"name":"Center for Vaccine Innovation and Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, Moores Cancer Center, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Medari","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, Moores Cancer Center, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Salu","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, Moores Cancer Center, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meza E","family":"Lucero","sequence":"additional","affiliation":[{"name":"Center for Vaccine Innovation and Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Brunel","sequence":"additional","affiliation":[{"name":"Center for Vaccine Innovation and Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Martsinkovskiy","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, Moores Cancer Center, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, Moores Cancer Center, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Gulay","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, Moores Cancer Center, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Jaljuli","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, Moores Cancer Center, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Mose","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, Moores Cancer Center, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.M","family":"Lowy","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, Moores Cancer Center, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CA","family":"Benedict","sequence":"additional","affiliation":[{"name":"Center for Vaccine Innovation and Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3805-9254","authenticated-orcid":false,"given":"T","family":"Hurtado de Mendoza","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, Moores Cancer Center, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041122330093000_2025.05.15.654308v1.1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.56.2736"},{"key":"2026041122330093000_2025.05.15.654308v1.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1606774"},{"key":"2026041122330093000_2025.05.15.654308v1.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1501824"},{"key":"2026041122330093000_2025.05.15.654308v1.4","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-0367"},{"key":"2026041122330093000_2025.05.15.654308v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/nature12477"},{"key":"2026041122330093000_2025.05.15.654308v1.6","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa4971"},{"key":"2026041122330093000_2025.05.15.654308v1.7","doi-asserted-by":"crossref","unstructured":"Evans, R. 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