Inhibition of PD-1 protein by the CRISPR-Cas9 method as antitumor therapy of non-small cell lung cancers

Abstract

Lung carcinoma is the second most common type of tumor in the world. Among them, 85% of the cases are of non-small cell lung cancer (NSCLC). It is known that, in general, NSCLC tumor cells proliferate due to a reduction in the cytotoxic T lymphocyte response. In the immune response to tumors, the interaction of the programmed death ligand 1 (PD-L1), expressed in tumor cells and the programmed cell death protein 1 (PD-1), expressed in cytotoxic T lymphocytes, promotes suppression of the immune response, leading to inhibition of the activation of cytotoxic T lymphocytes. Despite the biological therapies that have proven effective for the treatment of lung tumors, studies seek a genetic treatment option, such as the CRISPR/Cas9 method. This review aims to provide an update of the CRISPR-Cas9 method and its application as a therapeutic tool in NSCLC to deactivate the gene encoding the PD-1 protein. The genetic alteration of PD-1 protein by CRISPR-Cas9 can affect the interaction between receptor and ligand, allowing cytotoxic T lymphocytes to recognize and exert an antitumor response to NSCLC tumors.

CRISPER/CAS System, a Novel Tool of Targeted Therapy of Drug-resistant Lung Cancer

“…In one study, the gene encoding PD-1 protein was switched off by CRISPR-Cas9, which enhanced the anti-tumor activity of lymphocytes. 65 The beneficial effects of the CRISPR/Cas system in studying different aspects of LC such as tumor cell modeling, treatment, diagnosis, and drug resistance have been discussed below.…”