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Creation of PDX-Bearing Humanized Mice to Study Immuno-oncology

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Target Identification and Validation in Drug Discovery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1953))

Abstract

A significant obstacle to the study of human cancer biology and the testing of human specific immunotherapeutics is the paucity of translational models that recapitulate both the growth of human tumors and the functionality of human immune systems. Humanized mice engrafted with human hematopoietic stem cells (HSC) and patient-derived xenografts (PDX) enable preclinical investigation of the interactions between the human immune system and human cancer. We use immunodeficient non-obese diabetic (NOD, scid, gamma) NSG™ or NSG™-SGM3 mice as hosts for establishment of human immunity following HSC injection and for engraftment of human tumors. Here we describe a refined protocol for the subcutaneous implant of solid PDX tumors into humanized mice. Protocols to recover infiltrating immune cells from growing tumors and to evaluate the immune cell subsets by flow cytometry are also described.

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Acknowledgments

We thank Justin Jarvi and Marta Tewodros for trocar method development and technical assistance. This work was supported by The Jackson Laboratory.

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Authors and Affiliations

  1. Department of In Vivo Pharmacology Services, The Jackson Laboratory, Sacramento, CA, USA

    Li-Chin Yao, Mingshan Cheng, Pali Kaur & James G. Keck

  2. Department of Molecular Medicine and the Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA, USA

    Ken-Edwin Aryee & Michael A. Brehm

Authors
  1. Li-Chin Yao
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  2. Ken-Edwin Aryee
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  3. Mingshan Cheng
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  4. Pali Kaur
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  5. James G. Keck
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  6. Michael A. Brehm
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Corresponding author

Correspondence to Li-Chin Yao .

Editor information

Editors and Affiliations

  1. Pharmacology and Translational Research, Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria

    Jürgen Moll

  2. Department of Cancer Cell Signaling, Boehringer Ingelheim RCV GmBH & Co KG, Vienna, Austria

    Sebastian Carotta

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Yao, LC., Aryee, KE., Cheng, M., Kaur, P., Keck, J.G., Brehm, M.A. (2019). Creation of PDX-Bearing Humanized Mice to Study Immuno-oncology. In: Moll, J., Carotta, S. (eds) Target Identification and Validation in Drug Discovery. Methods in Molecular Biology, vol 1953. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-9145-7_15

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  • DOI: https://doi.org/10.1007/978-1-4939-9145-7_15

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-9144-0

  • Online ISBN: 978-1-4939-9145-7

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