CRISPR/Cas9-Mediated PD-1 Engineered T Cells: New Strategy to Block Tumor Immune Escape

Abstract

At present, overexpression of immune-related genes is one of the key mechanisms of tumor immune evasion. As a tumor cell-mediated immune escape core checkpoint molecule, the PD-L1 (programmed death ligand 1) will recruit SHP-1/SHP-2 (Src homology phosphotyrosyl phosphatase 1/ Src homology phosphotyrosyl phosphatase 2) phosphatase by interacting with PD-1 (Programmed Death 1) on T cells' surface, dephosphorylation of key molecules of the downstream signaling pathway of T cell receptors (TCR) (such as CD3ζ, ZAP70, PI3K/Akt), thereby inhibiting T cell expansion, cytokine secretion, cytotoxic particle release, and metabolic reprogramming. Eventually, it leads to T cell failure or apoptosis and directly inhibiting the anti-tumor function of T cells. Today, existing immune checkpoint blockade still has some problems during treatment, such as some patients do not respond or lose their efficacy due to drug resistance. According to the basic principles of PD-1 immune escape and the CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats associated protein 9) system, this paper explores the mechanism and advantages and disadvantages of the CRISPR/Cas9 technique in PD-1 expression inhibition combined with existing research, so as to provide a theoretical basis, summarize the shortcomings and future prospects for tumor immunotherapy Page layout.