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Application of Highly Immunocompromised Mice for the Establishment of Patient-Derived Xenograft (PDX) Models

1
Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 860-0811, Japan
2
Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan
3
Department of Biochemistry, Khon Kaen University, Khon Kaen 40002, Thailand
4
Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
*
Author to whom correspondence should be addressed.
Cells 2019, 8(8), 889; https://doi.org/10.3390/cells8080889
Received: 20 June 2019 / Revised: 9 August 2019 / Accepted: 9 August 2019 / Published: 13 August 2019
PDF [1346 KB, uploaded 13 August 2019]
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Abstract

Patient-derived xenograft (PDX) models are created by engraftment of patient tumor tissues into immunocompetent mice. Since a PDX model retains the characteristics of the primary patient tumor including gene expression profiles and drug responses, it has become the most reliable in vivo human cancer model. The engraftment rate increases with the introduction of Non-obese diabetic Severe combined immunodeficiency (NOD/SCID)-based immunocompromised mice, especially the NK-deficient NOD strains NOD/SCID/interleukin-2 receptor gamma chain(IL2Rγ)null (NOG/NSG) and NOD/SCID/Jak3(Janus kinase 3)null (NOJ). Success rates differ with tumor origin: gastrointestinal tumors acquire a higher engraftment rate, while the rate is lower for breast cancers. Subcutaneous transplantation is the most popular method to establish PDX, but some tumors require specific environments, e.g., orthotropic or renal capsule transplantation. Human hormone treatment is necessary to establish hormone-dependent cancers such as prostate and breast cancers. PDX mice with human hematopoietic and immune systems (humanized PDX) are powerful tools for the analysis of tumor–immune system interaction and evaluation of immunotherapy response. A PDX biobank equipped with patients’ clinical data, gene-expression patterns, mutational statuses, tumor tissue architects, and drug responsiveness will be an authoritative resource for developing specific tumor biomarkers for chemotherapeutic predictions, creating individualized therapy, and establishing precise cancer medicine.
Keywords: patient-derived xenograft; immunocompromised mice; precision medicine; drug screening; cancer; cell line; cancer immunotherapy; humanized mice patient-derived xenograft; immunocompromised mice; precision medicine; drug screening; cancer; cell line; cancer immunotherapy; humanized mice
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Okada, S.; Vaeteewoottacharn, K.; Kariya, R. Application of Highly Immunocompromised Mice for the Establishment of Patient-Derived Xenograft (PDX) Models. Cells 2019, 8, 889.

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