Researchers from Italy’s Ospedale San Raffaele Scientific Institute, in collaboration with Intellia Therapeutics, have used CRISPR to introduce multiple genomic edits to T cells, creating a T cell receptor therapy candidate with potent activity against haematological and solid tumours.
Professor Chiara Bonini and her team at the Ospedale San Raffaele Scientific Institute, in collaboration with Intellia Therapeutics, recently discovered a TCR specific to Wilm's tumour antigen 1 (WT1), a transcription factor involved in cell differentiation and growth, the expression of which is strongly linked to cancer development. The group explained that the WT1-specific TCR could be introduced into the patient's T cells to target a variety of cancers. In a paper published in Science Translational Medicine, the researchers describe the use of CRISPR-Cas9 technology to create several modifications in T cells to test various WT1-targeting TCRs, with promising results on tumour destruction in a range of cancer types. To create a TCR therapy capable of treating various types of cancer, the researchers had to find TCRs capable of recognising several WT1-derived epitopes with different HLA class I restrictions and with high avidity. The chosen receptor also had to be specific for WT1 epitopes that are naturally processed by the standard proteasome rather than the immunoproteasome, meaning that they are present in many cancers. Using CRISPR to introduce several genomic modifications into T cells, we have therefore created a candidate for T cell receptor therapy with potent activity against haematological and solid tumours.