Impact Factor 4.416

Frontiers journals are at the top of citation and impact metrics

Hypothesis and Theory ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2018.00559

Development of severe combined immunodeficient (SCID) pig models for translational cancer modeling: future insights on how humanized SCID pigs can improve preclinical cancer research

  • 1Iowa State University, United States
  • 2National Animal Disease Center (USDA ARS), United States

Abstract
Within the last decade there have been several severe combined immunodeficient (SCID) pig models discovered or genetically engineered. The animals have mutations in ARTEMIS, IL2RG, or RAG1/2 genes, or combinations thereof, providing SCID pigs with NK cells, but deficient in T and B cells, or deficient in NK, T, and B cells for research studies. Biocontainment facilities and positive pressure isolators are developed to limit pathogen exposure and prolong the life of SCID pigs. Raising SCID pigs in such facilities allows for completion of long-term studies such as xenotransplantation of human cells. Ectopically injected human cancer cell lines develop into tumors in SCID pigs, thus providing a human-sized in vivo model for evaluating imaging methods to improve cancer detection and therapeutic research and development. Immunocompromised pigs have the potential to be immunologically humanized by xenotransplantation with human hematopoietic stem cells, peripheral blood leukocytes, or fetal tissue. These cells can be introduced through various routes including injection into fetal liver or the intraperitoneal (IP) space, or into piglets by intravenous, IP, and intraosseous administration. The development and maintenance of transplanted human immune cells would be initially (at least) dependent on immune signaling from swine cells. Compared to mice, swine share higher homology in immune related genes with humans. We hypothesize that the SCID pig may be able to support improved engraftment and differentiation of a wide range of human immune cells as compared to equivalent mouse models. Humanization of SCID pigs would thus provide a valuable model system for researchers to study interactions between human tumor and human immune cells. Additionally, as the SCID pig model is further developed, it may be possible to develop patient-derived xenograft models for individualized therapy and drug testing. We thus theorize that the individualized therapeutic approach would be significantly improved with a humanized SCID pig due to similarities in size, metabolism, and physiology. In all, porcine SCID models have significant potential as an excellent preclinical animal model for therapeutic testing.

Keywords: Severe combined immnunodeficiency, Swine, Humanization, Cancer, Xenograft, Preclinical modeling

Received: 27 Aug 2018; Accepted: 09 Nov 2018.

Edited by:

Kyle Schachtschneider, University of Illinois at Chicago, United States

Reviewed by:

Saraswati Sukumar, School of Medicine, Johns Hopkins University, United States
Qingsheng Li, University of Nebraska-Lincoln, United States  

Copyright: © 2018 Boettcher, Loving, Cunnick and Tuggle. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Christopher K. Tuggle, Iowa State University, Ames, United States, cktuggle@iastate.edu