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Expansion and Adoptive Transfer of Human Vδ2+ T Cells to Assess Antitumor Effects In Vivo

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Cancer Immunosurveillance

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1884))

Abstract

Recent clinical trials have yielded promising results suggesting that γδ T cell62-based immunotherapies can be effective against hematological malignancies. Human T cells expressing Vγ9Vδ2+ receptors are particularly attractive candidates for this application, since they can be readily expanded in vitro in large quantities for adoptive transfer and do not require HLA-matching of donors and recipients. While it is well established that Vγ9Vδ2+ T cells are potently cytolytic against many human cancers and it has been shown that they can control transplanted human tumors in xenogeneic model systems, little is known about the parameters that determine the antitumor efficacy of adoptively transferred Vγ9Vδ2+ T cells in physiologically relevant scenarios. In particular, it may be important to separate their immunosurveillance functions from those employed in the context of an established tumor. Moreover, it is critical to understand how the presence of an immunosuppressive environment, such as one where tumor-infiltrating T cells are held in check by inhibitory ligands, affects the functions of Vγ9Vδ2+ T cells. This chapter describes how to establish Epstein-Barr virus (EBV) infection of human umbilical cord blood mononuclear cells (CBMCs) within immunodeficient mice, so as to drive the in vivo formation of human B cell lymphomas that contain an immunosuppressive environment. Details are provided on how to expand human Vγ9Vδ2+ T cells from peripheral blood mononuclear cells (PBMCs), administer them to the mice, and evaluate tumors and other tissues.

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Acknowledgments

Funding provided by a pilot grant from the University of Wisconsin Carbone Cancer Center that was supported in part by NIH grant NCI P30 CA014520, and by NIH grant R21 AI116007 and DoD CDMRP Award CA160396 to JEG; support for NAZ provided by T32 CA157322. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have no conflicting financial interests.

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  1. Akshat Sharma and Nicholas A. Zumwalde have contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Akshat Sharma, Nicholas A. Zumwalde & Jenny E. Gumperz

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  1. Akshat Sharma
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  2. Nicholas A. Zumwalde
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  3. Jenny E. Gumperz
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Correspondence to Jenny E. Gumperz .

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Editors and Affiliations

  1. Departamento de Biología Funcional, Inmunología, Universidad de Oviedo, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain

    Alejandro López-Soto

  2. Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Asturias, Spain

    Alicia R. Folgueras

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Sharma, A., Zumwalde, N.A., Gumperz, J.E. (2019). Expansion and Adoptive Transfer of Human Vδ2+ T Cells to Assess Antitumor Effects In Vivo. In: López-Soto, A., Folgueras, A. (eds) Cancer Immunosurveillance. Methods in Molecular Biology, vol 1884. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8885-3_4

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  • DOI: https://doi.org/10.1007/978-1-4939-8885-3_4

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