mesothelin-targeting universal chimeric antigen receptor T cells

Mesothelin-targeting universal chimeric antigen receptor T cells (Meso UCAR T-cells) are an investigational allogeneic CAR-T cell therapy developed by Cellectis. These 'off-the-shelf' cells are engineered from healthy donor T-cells using TALEN-based gene editing to target mesothelin (MSLN), a cell surface protein overexpressed in various solid tumors including mesothelioma, triple-negative breast cancer (TNBC), and pancreatic cancer. The engineering process involves the knockout of the T-cell receptor alpha constant (TRAC) to prevent graft-versus-host disease (GvHD) and the knockout of beta-2 microglobulin (B2M) to eliminate surface HLA-ABC expression, thereby protecting the cells from host-versus-graft (HvG) rejection. This dual-editing approach enhances the persistence and safety of the therapy in an allogeneic setting. Preclinical data suggests that Meso UCAR T-cells are particularly effective when used in combination with stromal-modulating therapies that deplete cancer-associated fibroblasts.

Other names

Mesothelin-targeting UCAR T-cellsMeso UCAR T-cellsUniversal Mesothelin CAR-T