Abstract: The present invention provides to the field of cell therapy, in particular, to adoptive T cell or NK cell therapy. It provides a human immunophilin knockout cell that is a T cell or NK cell, wherein the immunophilin is FKBP12 or cyclophilin A, or a cell population of such cells. The cell is resistant to the action of the immunosuppressant Tacrolimus and/or cyclosporine A. It is obtainable by CRISPR/Cas, e.g., CRISPR/Cas9-mediated knockout of the immunophilin or a derivate technology. The cell can be, e.g., a virus-specific cell, e.g., specific for an antigen from any of CMV, EBV, BKV, HPV, ADV, influenza virus, or SARS-CoV-2. It may also be a regulatory T cell.

Abstract: The invention relates to a method for determining T cell mediated immunity towards a CRISPR associated protein by contacting said cell preparation obtained from a patient with a CRISPR associated protein or a peptide mix that represents its amino acid sequence, or a cell manipulated to contain a CRISPR protein polypeptide to provide activated T cells. Subsequently, one or more subpopulations of said activated T cells are marked by specific ligand and counted, and a ratio (TREG/TEFF) of activated regulatory T cells to activated effector T cells is used to assess the immune status of the patient with respect to the CRISPR associated protein. The invention further relates to a method for generating a CRISPR associated protein specific Treg population and its use in therapy.