anti-programmed cell death protein 1 mesothelin-targeted chimeric antigen receptor T-cells

Anti-programmed cell death protein 1 mesothelin-targeted chimeric antigen receptor T-cells represent a novel cell therapy designed to treat solid tumors that express mesothelin (MSLN). Mesothelin is a tumor-associated antigen found in various cancers, including mesothelioma, ovarian, and pancreatic cancers. This CAR T-cell therapy is engineered to specifically recognize and target mesothelin-expressing tumor cells. A key feature of this therapy is its intrinsic modification to overcome the immunosuppressive effects of the programmed cell death protein 1 (PD-1) pathway within the tumor microenvironment. This can be achieved through various strategies, such as silencing PD-1 expression on the CAR T-cells (e.g., via CRISPR-Cas9 gene editing), incorporating a PD-1 dominant negative receptor into the CAR construct, or engineering the CAR T-cells to secrete PD-L1 blocking antibodies. By mitigating PD-1 mediated T-cell exhaustion, these engineered CAR T-cells aim to enhance their persistence, proliferation, and cytotoxic activity against solid tumors, addressing a significant challenge faced by conventional CAR T-cell therapies in solid tumor settings.