Exploiting the CRISPR‐Cas9 gene‐editing system for human cancers and immunotherapy

Abstract

The discovery of clustered regularly interspaced short palindromic repeats and CRISPR‐associated protein 9 (CRISPR‐Cas9) technology has brought advances in the genetic manipulation of eukaryotic cells, which has revolutionised cancer research and treatment options. It is increasingly being used in cancer immunotherapy, including adoptive T and natural killer (NK) cell transfer, secretion of antibodies, cytokine stimulation and overcoming immune checkpoints. CRISPR‐Cas9 technology is used in autologous T cells and NK cells to express various innovative antigen designs and combinations of chimeric antigen receptors (CARs) targeted at specific antigens for haematological and solid tumors. Additionally, advanced engineering in immune cells to enhance their sensing circuits with sophisticated functionality is now possible. Intensive research on the CRISPR‐Cas9 system has provided scientists with the ability to overcome the hostile tumor microenvironment and generate more products for future clinical use, especially off‐the‐shelf, universal cellular products, bringing exciting milestones for immunotherapy. This review discussed the application and challenges of CRISPR technology in cancer research and immunotherapy, its advances and prospects for promoting new cell‐based therapeutic beyond immune oncology.

Suppression of protein quality control system by TRIM30a sensitises tumour cells to NK cell‐mediated immune surveillance

“…We further corroborated these findings using Rag1 −/− mice and observed the original disparities in tumour growth kinetics in these mice, indicating that NK cells, but not B or T cells, mediate the suppressive effect on TRIM30a‐expressing tumour cells. NK cells are highly effective at eliminating tumour cells through a variety of mechanisms [4], and our findings suggest that TRIM30a overexpression in tumour cells may resulte in immunoediting of their immunogens (ligands) that are specific for NK cell activation. Our data on the increased in vivo and in vitro cytolysis of TRIM30a‐expressing tumour cells by NK cells further support that TRIM30a expression facilitates tumour cytolysis by NK cells.…”

“…They are also important in facilitating the adaptive immune response since they are the first line of host defence, and NK cell immunotherapy has gained attention as a viable alternative against several tumours in the clinic. Recent advancements in NK cell adoptive transfer and checkpoint blockade have highlighted the potential of NK‐based immunotherapy, which has yet to be fully realised [3, 4]. The complex architecture of the tumour microenvironment has prevented the full exploitation of NK cells immunotherapy, and approaches to overcome NK cell exhaustion and harness its full antitumor potential may revolutionise cancer treatment.…”

Recent advances and applications of CRISPR-Cas9 in cancer immunotherapy

“…Critical understanding of multiple modes of anergy, exhaustion, and senescence, such as reduction of effector cytokines or impairment of cytotoxicity, presence of inhibitory cytokines, regulatory immune cells, and dysregulated receptor signaling found in TME [ 114 ], will guide design patterns to enhance NK cell functions. In accordance with these, reactivation of NK cells engineering with CRISPR-Cas9 is an appreciable immunotherapeutic approach.…”

Artificial Intelligence and Machine Learning in Cancer Research: A Systematic and Thematic Analysis of the Top 100 Cited Articles Indexed in Scopus Database

“…Lung cancer remains the leading cause of cancer death, with an estimated 1.8 million deaths, followed by colorectal, liver, stomach, and breast cancers. 2 Treatment and prevention measures of cancer are still challenging 3 , 4 , but the emergence of artificial intelligence (AI) and machine learning (ML) positively supports treatment and control of cancer. 5 , 6 …”

“…Lung cancer remains the leading cause of cancer death, with an estimated 1.8 million deaths, followed by colorectal, liver, stomach, and breast cancers. 2 Treatment and prevention measures of cancer are still challenging 3,4 , but the emergence of artificial intelligence (AI) and machine learning (ML) positively supports treatment and control of cancer. 5,6 Recently, the increasing knowledge of AI techniques caused significant positive waves in healthcare by gradually altering the global landscape of healthcare and biomedical research.…”