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

Faisal Iqbal

doi:10.53730/ijhs.v7nS1.14397

Authors

Faisal Iqbal
faisalsaleh59@ymail.com
Department of Biological Sciences, International Islamic University, Islamabad, Pakistan

Keywords:

CAR T cells, Cas9 RNP, PD-1, PD-L1, CRISPR/Cas9

Abstract

CAR T cell therapy is a cutting-edge method of treating cancer that entails altering a patient’s own T cells to improve their capacity to combat cancer cells. This is accomplished by giving the T cells chimeric antigen receptors (CARs), which give them ability to recognize and precisely target cancer cells. T cells from the patient are first removed, and then their genes are modified to include CARs. The modified T cells are then reintroduced to the patient's body where they can more successfully target and eliminate cancer cells. CAR T cell immunotherapies and checkpoint inhibitors, notably PD-1 antagonists, have emerged as promising cancer therapeutic modalities. In this study, a novel method for producing PD-1-deficient anti-CD19 CAR T cells was devised, which combines lentiviral transduction with Cas9 ribonucleoprotein (Cas9 RNP)-mediated gene editing. The modified CAR T cells showed enhanced clearance of PDL1+ tumor xenograft in live animal models and higher efficacy in killing tumor cells in laboratory trials by interrupting the Pdcd1 (PD-1) gene. The combined effects of PD-1 disruption and CAR T cell therapy have the potential to significantly improve cancer immunotherapy.

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