Establishing an immunocompromised porcine model of human cancer for novel therapy development with pancreatic adenocarcinoma and irreversible electroporation

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dc.contributor.authorHendricks-Wenger, Alissaen
dc.contributor.authorAycock, Kenneth N.en
dc.contributor.authorNagai-Singer, Margaret A.en
dc.contributor.authorCoutermarsh-Ott, Sherylen
dc.contributor.authorLorenzo, Melvin F.en
dc.contributor.authorGannon, Jessicaen
dc.contributor.authorUh, Kyungjunen
dc.contributor.authorFarrell, Kaylaen
dc.contributor.authorBeitel-White, Natalieen
dc.contributor.authorBrock, Rebecca M.en
dc.contributor.authorSimon, Alexanderen
dc.contributor.authorMorrison, Holly A.en
dc.contributor.authorTuohy, Joanne L.en
dc.contributor.authorClark-Deener, Sherrieen
dc.contributor.authorVlaisavljevich, Elien
dc.contributor.authorDavalos, Rafael V.en
dc.contributor.authorLee, Kihoen
dc.contributor.authorAllen, Irving C.en
dc.contributor.departmentBiomedical Engineering and Mechanicsen
dc.contributor.departmentVirginia Tech Carilion School of Medicineen
dc.contributor.departmentLarge Animal Clinical Sciencesen
dc.contributor.departmentSmall Animal Clinical Sciencesen
dc.contributor.departmentMechanical Engineeringen
dc.contributor.departmentAnimal and Poultry Sciencesen
dc.contributor.departmentElectrical and Computer Engineeringen
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.contributor.departmentInstitute for Critical Technology and Applied Scienceen
dc.date.accessioned2021-08-13T17:15:26Zen
dc.date.available2021-08-13T17:15:26Zen
dc.date.issued2021-04-07en
dc.date.updated2021-08-13T17:15:21Zen
dc.description.abstractNew therapies to treat pancreatic cancer are direly needed. However, efficacious interventions lack a strong preclinical model that can recapitulate patients’ anatomy and physiology. Likewise, the availability of human primary malignant tissue for ex vivo studies is limited. These are significant limitations in the biomedical device field. We have developed RAG2/IL2RG deficient pigs using CRISPR/Cas9 as a large animal model with the novel application of cancer xenograft studies of human pancreatic adenocarcinoma. In this proof-of-concept study, these pigs were successfully generated using on-demand genetic modifications in embryos, circumventing the need for breeding and husbandry. Human Panc01 cells injected subcutaneously into the ears of RAG2/IL2RG deficient pigs demonstrated 100% engraftment with growth rates similar to those typically observed in mouse models. Histopathology revealed no immune cell infiltration and tumor morphology was highly consistent with the mouse models. The electrical properties and response to irreversible electroporation of the tumor tissue were found to be similar to excised human pancreatic cancer tumors. The ample tumor tissue produced enabled improved accuracy and modeling of the electrical properties of tumor tissue. Together, this suggests that this model will be useful and capable of bridging the gap of translating therapies from the bench to clinical application.en
dc.description.versionPublished versionen
dc.format.extent14 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifierARTN 7584 (Article number)en
dc.identifier.doihttps://doi.org/10.1038/s41598-021-87228-5en
dc.identifier.eissn2045-2322en
dc.identifier.issn2045-2322en
dc.identifier.issue1en
dc.identifier.orcidDavalos, Rafael [0000-0003-1503-9509]en
dc.identifier.orcidClark-Deener, Sherrie [0000-0002-6620-0625]en
dc.identifier.orcidAllen, Irving [0000-0001-9573-5250]en
dc.identifier.other10.1038/s41598-021-87228-5 (PII)en
dc.identifier.pmid33828203 (pubmed)en
dc.identifier.urihttp://hdl.handle.net/10919/104640en
dc.identifier.volume11en
dc.language.isoenen
dc.publisherNature Researchen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000640391700021&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjecttumor xenograftsen
dc.subjectablationen
dc.subjectmouseen
dc.subjectgemcitabineen
dc.subjectsafetyen
dc.subjectmiceen
dc.subjectpigsen
dc.subjectimmunodeficiencyen
dc.subjectchemotherapyen
dc.subjectfeasibilityen
dc.titleEstablishing an immunocompromised porcine model of human cancer for novel therapy development with pancreatic adenocarcinoma and irreversible electroporationen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2021-03-25en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Engineeringen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Large Animal Clinical Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciencesen
pubs.organisational-group/Virginia Tech/Engineering/Biomedical Engineering and Mechanicsen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Engineering/COE T&R Facultyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciences/Durelle Scotten

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