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

Abstract New 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 signi...

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Autores principales:	Alissa Hendricks-Wenger, Kenneth N. Aycock, Margaret A. Nagai-Singer, Sheryl Coutermarsh-Ott, Melvin F. Lorenzo, Jessica Gannon, Kyungjun Uh, Kayla Farrell, Natalie Beitel-White, Rebecca M. Brock, Alexander Simon, Holly A. Morrison, Joanne Tuohy, Sherrie Clark-Deener, Eli Vlaisavljevich, Rafael V. Davalos, Kiho Lee, Irving C. Allen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7c98b8b06db5461383bdd6c59844f1fa
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spelling	oai:doaj.org-article:7c98b8b06db5461383bdd6c59844f1fa2021-12-02T14:20:43ZEstablishing an immunocompromised porcine model of human cancer for novel therapy development with pancreatic adenocarcinoma and irreversible electroporation10.1038/s41598-021-87228-52045-2322https://doaj.org/article/7c98b8b06db5461383bdd6c59844f1fa2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87228-5https://doaj.org/toc/2045-2322Abstract New 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.Alissa Hendricks-WengerKenneth N. AycockMargaret A. Nagai-SingerSheryl Coutermarsh-OttMelvin F. LorenzoJessica GannonKyungjun UhKayla FarrellNatalie Beitel-WhiteRebecca M. BrockAlexander SimonHolly A. MorrisonJoanne TuohySherrie Clark-DeenerEli VlaisavljevichRafael V. DavalosKiho LeeIrving C. AllenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alissa Hendricks-Wenger Kenneth N. Aycock Margaret A. Nagai-Singer Sheryl Coutermarsh-Ott Melvin F. Lorenzo Jessica Gannon Kyungjun Uh Kayla Farrell Natalie Beitel-White Rebecca M. Brock Alexander Simon Holly A. Morrison Joanne Tuohy Sherrie Clark-Deener Eli Vlaisavljevich Rafael V. Davalos Kiho Lee Irving C. Allen Establishing an immunocompromised porcine model of human cancer for novel therapy development with pancreatic adenocarcinoma and irreversible electroporation
description	Abstract New 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.
format	article
author	Alissa Hendricks-Wenger Kenneth N. Aycock Margaret A. Nagai-Singer Sheryl Coutermarsh-Ott Melvin F. Lorenzo Jessica Gannon Kyungjun Uh Kayla Farrell Natalie Beitel-White Rebecca M. Brock Alexander Simon Holly A. Morrison Joanne Tuohy Sherrie Clark-Deener Eli Vlaisavljevich Rafael V. Davalos Kiho Lee Irving C. Allen
author_facet	Alissa Hendricks-Wenger Kenneth N. Aycock Margaret A. Nagai-Singer Sheryl Coutermarsh-Ott Melvin F. Lorenzo Jessica Gannon Kyungjun Uh Kayla Farrell Natalie Beitel-White Rebecca M. Brock Alexander Simon Holly A. Morrison Joanne Tuohy Sherrie Clark-Deener Eli Vlaisavljevich Rafael V. Davalos Kiho Lee Irving C. Allen
author_sort	Alissa Hendricks-Wenger
title	Establishing an immunocompromised porcine model of human cancer for novel therapy development with pancreatic adenocarcinoma and irreversible electroporation
title_short	Establishing an immunocompromised porcine model of human cancer for novel therapy development with pancreatic adenocarcinoma and irreversible electroporation
title_full	Establishing an immunocompromised porcine model of human cancer for novel therapy development with pancreatic adenocarcinoma and irreversible electroporation
title_fullStr	Establishing an immunocompromised porcine model of human cancer for novel therapy development with pancreatic adenocarcinoma and irreversible electroporation
title_full_unstemmed	Establishing an immunocompromised porcine model of human cancer for novel therapy development with pancreatic adenocarcinoma and irreversible electroporation
title_sort	establishing an immunocompromised porcine model of human cancer for novel therapy development with pancreatic adenocarcinoma and irreversible electroporation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7c98b8b06db5461383bdd6c59844f1fa
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Establishing an immunocompromised porcine model of human cancer for novel therapy development with pancreatic adenocarcinoma and irreversible electroporation

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