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PD-1-knockout CD19 CAR-T cells are an investigational adoptive cell therapy developed by the Sun Yat-sen University Cancer Center for the treatment of relapsed or refractory B-cell non-Hodgkin lymphoma. This therapy involves autologous T cells that are genetically engineered to express a chimeric antigen receptor (CAR) specific for the B-cell antigen CD19. Additionally, the cells undergo CRISPR/Cas9-mediated genome editing to knock out the programmed cell death protein 1 (PD-1) gene (PDCD1). The removal of PD-1 is designed to prevent the inhibitory signaling that typically leads to T-cell exhaustion in the tumor microenvironment, thereby improving the persistence and cytotoxic efficacy of the CAR-T cells against lymphoma cells. Clinical trials have demonstrated the feasibility and safety of this approach in patients with various B-cell malignancies.
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