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Methods Mol Biol. 2020;2115:407-417. doi: 10.1007/978-1-0716-0290-4_22.

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

Author information

1
Department of Cellular Therapy, Department of Oncology, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.
2
Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway. mouldy.sioud@rr-research.no.

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.

KEYWORDS:

Adoptive T cell therapy; CRISPR-Cas9; Chimeric antigen receptor; Gene editing; Graft-versus-host disease (GvHD); T cell receptor; Tumor infiltrating lymphocytes

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