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

• Published in: Methods in molecular biology (Clifton, N.J.) Vol. 2115; p. 407
• Main Authors: Wälchli, Sébastien, Sioud, Mouldy
• Format: Journal Article
• Language: English
• Published: United States 01.01.2020
• Subjects: Animals; CRISPR-Cas Systems; Gene Editing - methods; Humans; Immunotherapy, Adoptive - adverse effects; Immunotherapy, Adoptive - methods; T-Lymphocytes - metabolism; T-Lymphocytes - transplantation; T cell receptor; Tumor infiltrating lymphocytes; Chimeric antigen receptor; Adoptive T cell therapy; CRISPR-Cas9; Gene editing; Graft-versus-host disease (GvHD)
• ISSN: 1940-6029
• DOI: 10.1007/978-1-0716-0290-4_22

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.