CRISPR-Cas9-Mediated Glucocorticoid Resistance in Virus-Specific T Cells for Adoptive T Cell Therapy Posttransplantation.

ABSTRACT: Immunosuppression posttransplantation exposes patients to an increased risk for refractory viral infections as an important cause of morbidity and mortality. Protective T cell immunity can be restored by adoptive T cell transfer, but ongoing immunosuppression limits efficacy of T cell responses. In order to deliver protection against viral pathogens and allow at the same time necessary steroid therapy, we generated glucocorticoid-resistant T cells by CRISPR-Cas9-mediated knockout of the glucocorticoid receptor in primary human virus-specific T cell products. Characterization of the T cell product revealed high efficiency of glucocorticoid receptor knockout and high purity of virus-specific T cells. This tandem T cell engineering preserved protective T cell functionality, such as cytotoxici

SUBMITTER: Kaeuferle T 

PROVIDER: S-EPMC7474265 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature