RNF166-overexpressing T-cells

RNF166-overexpressing T-cells represent an adoptive T-cell therapy engineered to enhance the persistence and cytotoxic function of T-cells, particularly in the challenging tumor microenvironment of solid tumors. This novel approach addresses T-cell exhaustion (TEX), a major limitation in current cancer immunotherapies. By overexpressing RNF166, an E3 ubiquitin ligase, these T-cells undergo proteostasis remodeling, leading to the destabilization of inhibitory receptors and stabilization of costimulatory receptors. This engineering significantly prolongs the T-cells' ability to control tumor growth and has shown to enhance the persistence of CAR T-cells in vitro. Elevated RNF166 expression in tumor-infiltrating lymphocytes has also been correlated with improved responses to immune checkpoint blockade in metastatic melanoma, suggesting its potential as a strategy to improve the efficacy of adoptive cell therapies.