Although clinicians have successfully used CAR-T cells in cancer, many patients experience a cancer relapse caused by the hostile environment created by the cancer cells. After repeated encounters with cancer cells, CAR-T cells lose their ability to effectively divide and attack the tumour. Therefore, a research team used CRISPR screening to identify potential genes that could improve CAR-T cell therapy. The researchers found that knocking out the CUL5 gene improved the growth and longevity of CAR-T cells, even after repeated exposure to cancer cells. The gene of interest, CUL5, is involved in the degradation of specific proteins inside cells. When this gene is inactive, a cell signalling pathway known as the JAK-STAT signalling pathway becomes more sustained. This pathway sends signals encouraging T lymphocytes to grow and multiply, making them more effective at fighting cancer. Therefore, a new way of partially reducing CUL5 activity has been developed by using a virus to deliver genetic material to CAR-T cells.
