SOX4KO.M5CAR

SOX4KO.M5CAR is an experimental chimeric antigen receptor (CAR) T-cell therapy targeting mesothelin (MSLN), engineered with a CRISPR-mediated knockout of the transcription factor SOX4. Developed by researchers at the University of Pennsylvania and the University of California San Francisco, this modification is designed to mitigate T-cell exhaustion, a significant barrier to the efficacy of CAR T-cell therapies in solid tumors. Chronic antigen exposure in the tumor microenvironment typically induces a dysfunctional, NK-like phenotype in CAR T cells, leading to reduced proliferation and cytotoxicity. By disrupting SOX4, which has been identified as a key driver of this exhaustion signature, the therapy aims to maintain robust anti-tumor activity and improved persistence. Preclinical studies in pancreatic cancer models have demonstrated that SOX4-knockout CAR T cells exhibit enhanced cytotoxicity and a reduced dysfunctional gene expression profile compared to standard mesothelin-targeted CAR T cells.

Other names

SOX4-knockout mesothelin-targeted CAR T cellsSOX-4-knockout mesothelin-targeted CAR T cellsSOX 4-knockout mesothelin-targeted CAR T cells