Enhancing the effectiveness of Chimeric Antigen Receptor (CAR) T cells against tumors through CRISPR/Cas9-mediated PD-1 disruption

Immunotherapies involving chimeric antigen receptor (CAR) T cells and checkpoint inhibitors, such as programmed cell death protein 1 (PD-1) antagonists, have shown promise in treating cancer. The combined benefits of these medicines are yet not fully understood. In this work, it was discovered that human CAR become hypo-functional due to the expression ligand (PD-L1) on tumor cells, which reduces their efficacy a sub-cutaneous xenograft model. To solve problem, scientists created procedure combines lentiviral transduction with Cas9 ribonucleoprotein (Cas9 RNP)-mediated gene editing produce PD-1-deficient anti-CD19 cells. Disrupting Pdcd1 led increased killing vitro improved clearance PDL1+ vivo. This study highlights potential precision genome engineering enhance next-generation therapies improve immunotherapy.