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Analysis of Antitumor Effects of CAR-T Cells in Mice with Solid Tumors

  • Alba Rodriguez-Garcia
  • Keisuke Watanabe
  • Sonia GuedanEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 2086)

Abstract

Animal models provide an essential tool to study the efficacy of CAR-T cell treatments. Most of the current works test human CAR-T cells in immunodeficient animals, typically NOD Scid Gamma (NSG) mice transplanted with human tumors. Despite the limitations of this model, including the difficulty to study the interaction between CAR-T cells and the human innate system and to assess the toxicity of this therapy, NSG are extensively used for adoptive T cell transfer studies. In this chapter, we will describe the protocols to test CAR-T cells in NSG animals with solid tumors. We first describe the implantation of human xenograft tumors in NSG animals, followed by CAR-T cell administration and assessment of antitumor responses. We will also review the protocols to analyze T cell persistence in the blood of treated animals. Finally, we will focus on the analysis of the tumors at the end point of the experiment, including the percentage, phenotype, and function of tumor infiltrating T cells, and loss of antigen expression.

Key words

Chimeric antigen receptors (CAR) Adoptive T cell transfer (ACT) NSG animals Tumor xenograft T cell persistence T cell exhaustion 

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Alba Rodriguez-Garcia
    • 1
  • Keisuke Watanabe
    • 2
  • Sonia Guedan
    • 3
    Email author
  1. 1.Center for Cellular ImmunotherapiesPerelman School of Medicine, University of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of Hematology and OncologyNagoya University Graduate School of MedicineNagoyaJapan
  3. 3.Department of Hematology and OncologyHospital Clinic, Institut d’Investigacions BiomÒdiques August Pi i Sunyer (IDIBAPS)BarcelonaSpain

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