Abstract: The invention provides a modified T cell, or an isolated population of immune cells expressing a CXCR3 isoform selected from CXCR3A, CXCR3B, and CXCR3alt, and optionally, further expressing transgenes comprising an artificial T cell receptor, and/or a CXCR3 ligand, for use as a medicament. The invention also provides the methods to obtain said cells, or populations of cells from a plurality of immune cells derived from a human subject. The invention also relates to assessment of CXCR3 splice variants and its ligands CXCL9, CXCL10, and CXCL11 in muscle-invasive bladder cancer (MIBC) patients, to enable patients to be stratified for their predicted response to a chemotherapy drug treatment, or clinical outcome.

Abstract: A nucleic acid construct for targeting and integrating a CD3 zeta-deficient chimeric antigen receptor (CAR) fragment into an endogenous CD3 zeta/CD247 gene of a host genome. Also disclosed is a genetically modified human cell expressing an exogenous nucleic acid sequence encoding a CD3 zeta deficient CAR fragment, integrated in-frame into the endogenous CD3 zeta/CD247 gene for gene fusion, to form a functional CAR including an exogenous CAR fragment fused with an endogenous CD3 zeta domain.

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.