The Application of CRISPR/Cas9 Technology for Cancer Immunotherapy: Current Status and Problems.

Luyao Wang,Yurong Chen,Xiangpeng Dai,Ziyi Li,Xinrui Liu

doi:10.3389/fonc.2021.704999

Abstract

Cancer is one of the main causes of disease-related deaths in the world. Although cancer treatment strategies have been improved in recent years, the survival time of cancer patients is still far from satisfied. Cancer immunotherapy, such as Oncolytic virotherapy, Immune checkpoints inhibition, Chimeric antigen receptor T (CAR-T) cell therapy, Chimeric antigen receptor natural killer (CAR-NK) cell therapy and macrophages genomic modification, has emerged as an effective therapeutic strategy for different kinds of cancer. However, many patients do not respond to the cancer immunotherapy which warrants further investigation to optimize this strategy. The clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9), as a versatile genome engineering tool, has become popular in the biology research field and it was also applied to optimize tumor immunotherapy. Moreover, CRISPR-based high-throughput screening can be used in the study of immunomodulatory drug resistance mechanism. In this review, we summarized the development as well as the application of CRISPR/Cas9 technology in the cancer immunotherapy and discussed the potential problems that may be caused by this combination.

Highlights

Given that the incidence of cancer is gradually increasing even with the improved prognosis techniques [1], methods for cancer therapy are widely investigated and the chemotherapy, radiotherapy and surgery are commonly used to prolong survival time of cancer patients
There are many issues that should be considered in the application of Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system in immunotherapy, such as off-target effect, editing efficiency and clinical safety which provide challenges to researchers
Studies indicated that the offtarget mutagenesis mediated by CRISPR/Cas9 may be different due to different single guide RNA (sgRNA) design and target sequences [101]

Summary

Introduction

Given that the incidence of cancer is gradually increasing even with the improved prognosis techniques [1], methods for cancer therapy are widely investigated and the chemotherapy, radiotherapy and surgery are commonly used to prolong survival time of cancer patients. Chimeric antigen receptor T therapy, immune checkpoints blockade and genetically engineered macrophages have provided multi-mode methods to target and destroy cancer cells. Using CRISPR/Cas9 technology to knock out immune checkpoints such as programmed death-1 (PD-1), programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) may provide a new direction for cancer immunotherapy [15].

Results

Conclusion