Following on from these findings, a mesothelin-specific CAR T cell expressing CD3-zeta, CD28, and the caspase-9 safety gene was evaluated as loco-regional therapy delivered intra-pleurally in patients with aggressive pleural malignancy (breast cancer, lung cancer, and mesothelioma) with cyclophosphamide preconditioning; remarkably, patients receiving concurrent anti PD-1 therapy with pembrolizumab achieved a median overall survival of 24 months [91]. Here, CD28 is linked to lung carcinoma.