Establishing an immunocompromised porcine model of human cancer for novel therapy development with pancreatic adenocarcinoma and irreversible electroporation. Hendricks-Wenger, A., Aycock, K. N., Nagai-Singer, M. A., Coutermarsh-Ott, S., Lorenzo, M. F., Gannon, J., Uh, K., Farrell, K., Beitel-White, N., Brock, R. M., Simon, A., Morrison, H. A., Tuohy, J., Clark-Deener, S., Vlaisavljevich, E., Davalos, R. V., Lee, K., & Allen, I. C. Sci Rep, 11(1):7584, 2021. 2045-2322 Hendricks-Wenger, Alissa Aycock, Kenneth N Nagai-Singer, Margaret A Coutermarsh-Ott, Sheryl Lorenzo, Melvin F Gannon, Jessica Uh, Kyungjun Farrell, Kayla Beitel-White, Natalie Brock, Rebecca M Simon, Alexander Morrison, Holly A Tuohy, Joanne Clark-Deener, Sherrie Vlaisavljevich, Eli Davalos, Rafael V Lee, Kiho Allen, Irving C P01 CA207206/CA/NCI NIH HHS/United States R21 EB028429/EB/NIBIB NIH HHS/United States R01 CA213423/CA/NCI NIH HHS/United States R21 OD027062/OD/NIH HHS/United States R01 CA240476/CA/NCI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2021/04/09 Sci Rep. 2021 Apr 7;11(1):7584. doi: 10.1038/s41598-021-87228-5.doi abstract bibtex 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.
@article{RN119,
author = {Hendricks-Wenger, A. and Aycock, K. N. and Nagai-Singer, M. A. and Coutermarsh-Ott, S. and Lorenzo, M. F. and Gannon, J. and Uh, K. and Farrell, K. and Beitel-White, N. and Brock, R. M. and Simon, A. and Morrison, H. A. and Tuohy, J. and Clark-Deener, S. and Vlaisavljevich, E. and Davalos, R. V. and Lee, K. and Allen, I. C.},
title = {Establishing an immunocompromised porcine model of human cancer for novel therapy development with pancreatic adenocarcinoma and irreversible electroporation},
journal = {Sci Rep},
volume = {11},
number = {1},
pages = {7584},
note = {2045-2322
Hendricks-Wenger, Alissa
Aycock, Kenneth N
Nagai-Singer, Margaret A
Coutermarsh-Ott, Sheryl
Lorenzo, Melvin F
Gannon, Jessica
Uh, Kyungjun
Farrell, Kayla
Beitel-White, Natalie
Brock, Rebecca M
Simon, Alexander
Morrison, Holly A
Tuohy, Joanne
Clark-Deener, Sherrie
Vlaisavljevich, Eli
Davalos, Rafael V
Lee, Kiho
Allen, Irving C
P01 CA207206/CA/NCI NIH HHS/United States
R21 EB028429/EB/NIBIB NIH HHS/United States
R01 CA213423/CA/NCI NIH HHS/United States
R21 OD027062/OD/NIH HHS/United States
R01 CA240476/CA/NCI NIH HHS/United States
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
England
2021/04/09
Sci Rep. 2021 Apr 7;11(1):7584. doi: 10.1038/s41598-021-87228-5.},
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.},
keywords = {Adenocarcinoma/pathology/physiopathology/*therapy
Animals
CRISPR-Cas Systems
Cell Line, Tumor
DNA-Binding Proteins/deficiency/genetics/immunology
Electric Conductivity
Electroporation/*methods
Female
Gene Knockout Techniques
Humans
Immunocompromised Host
Interleukin Receptor Common gamma Subunit/deficiency/genetics/immunology
Male
Mice
Pancreatic Neoplasms/pathology/physiopathology/*therapy
Proof of Concept Study
Swine
Translational Research, Biomedical
Xenograft Model Antitumor Assays},
ISSN = {2045-2322},
DOI = {10.1038/s41598-021-87228-5},
year = {2021},
type = {Journal Article}
}
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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. 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