TNC-CAR T cells

TNC-CAR T cells are an experimental chimeric antigen receptor (CAR) T-cell therapy designed to target the FNIII-D domain of Tenascin-C (TNC), an extracellular matrix protein that is highly overexpressed in glioblastoma (GBM) and other solid tumors. The CAR construct utilizes a humanized single-chain variable fragment (scFv) derived from the R6N antibody, coupled with a CD28 costimulatory domain and a CD3ζ signaling domain. Unlike traditional CAR-T therapies that target cell-surface antigens, TNC-CAR T cells target a component of the tumor microenvironment. This approach allows the cells to mediate "bystander killing" of antigen-negative tumor cells by recognizing soluble TNC or TNC bound to neighboring cells. Preclinical studies in patient-derived GBM xenografts have demonstrated significant antitumor activity and localized apoptosis, although efficacy can be limited by early T-cell exhaustion. Research indicates that combining TNC-CAR T cells with immune checkpoint inhibitors (targeting PD-1, TIM-3, and LAG-3) can significantly enhance therapeutic outcomes.

Other names

Tenascin-C-targeted CAR T cellsanti-TNC CAR T cells