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Next Generation of Adoptive T Cell Therapy Using CRISPR/Cas9 Technology: Universal or Boosted?

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RNA Interference and CRISPR Technologies

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2115))

Abstract

Adoptive T cell therapy (ACT) using either chimeric antigen receptor (CAR)- or T cell receptor (TCR)-engineered lymphocytes has emerged as a promising strategy to treat cancer. However, this therapy is still facing enormous challenges such as poor quality of autologous T cells, T cell exhaustion, and the immune suppressive tumor microenvironments. Additionally, graft-versus-host disease is an issue that must be addressed to allow the use of allogeneic T cells. Strategies to overcome these therapeutic challenges using gene editing technology are now being developed. One strategy is to disrupt TCR and/or MHC expression in healthy donor T cells to generate T cells for universal use. Another strategy is to improve the quality of patient’s T cells by eliminating either the expression of selected immune checkpoint receptors or negative regulators of TCR signaling and/or T-cell homeostasis. Here, we review the use of CRISPR-Cas9 platform in T cell engineering with a focus on the development of universal T cells and boosted autologous cells for next-generation ACT.

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Acknowledgments

This work was supported by the Norwegian Cancer Society and South-Eastern Norway Regional Health Authority.

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Authors and Affiliations

  1. Department of Cellular Therapy, Department of Oncology, Oslo University Hospital-Radiumhospitalet, Oslo, Norway

    Sébastien Wälchli

  2. Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway

    Mouldy Sioud

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  1. Sébastien Wälchli
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  2. Mouldy Sioud
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Correspondence to Mouldy Sioud .

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Editors and Affiliations

  1. Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway

    Mouldy Sioud

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Wälchli, S., Sioud, M. (2020). Next Generation of Adoptive T Cell Therapy Using CRISPR/Cas9 Technology: Universal or Boosted?. In: Sioud, M. (eds) RNA Interference and CRISPR Technologies. Methods in Molecular Biology, vol 2115. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0290-4_22

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  • DOI: https://doi.org/10.1007/978-1-0716-0290-4_22

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0289-8

  • Online ISBN: 978-1-0716-0290-4

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