Abstract

ImmTAX (Immune mobilising monoclonal T cell receptors (TCR) against X disease) molecules are a novel class of T cell engaging bispecific proteins developed for the treatment of cancer, infectious and autoimmune diseases. ImmTAX molecules target intracellularly processed disease-specific peptides presented at the cell surface in the context of class I human leukocyte antigen (HLA) molecules. In cancer, ImmTAC (Immune mobilising monoclonal T cell receptors against cancer) molecules bind to tumour cells via a TCR, engineered with high affinity to a tumour specific peptide-HLA target. The anti-CD3 effector function of the ImmTAC molecule redirects T cells to the tumour resulting in potent T cell activation and tumour cell lysis. Here we present the use of CRISPR/Cas9 gene editing as a powerful approach to evaluate soluble bispecific ImmTAC molecules by generating cell models to assess potency and specificity including non-immunogenic knock-out of peptide targets in cancer cell lines for specificity testing, and HLA converted cell lines to evaluate HLA restriction and increase available HLA-relevant, target positive cell lines.