Emerging role of RNA interference in immune cells engineering and its therapeutic synergism in immunotherapy

被引：13

作者：

Monty, Masuma Akter ^{[1
]}

Islam, Md. Ariful ^{[2
]}

Nan, Xu ^{[1
]}

Tan, Jingwen ^{[1
]}

Tuhin, Israth Jahan ^{[1
]}

Tang, Xiaowen ^{[3
]}

Miao, Miao ^{[3
]}

Wu, Depei ^{[3
]}

Yu, Lei ^{[1
]}

机构：

[1] East China Normal Univ, Sch Chem & Mol Engn, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, Inst Biomed Engn & Technol, Shanghai 200062, Peoples R China

[2] Shanghai Jiao Tong Univ, Sch Pharm, Shanghai, Peoples R China

[3] Soochow Univ, Affiliated Hosp 1, Suzhou 215006, Jiangsu, Peoples R China

来源：

BRITISH JOURNAL OF PHARMACOLOGY | 2021年 / 178卷 / 08期

关键词：

cancer immunotherapy; combinatorial RNAi; gene silencing; RNA interference (RNAi); RNAi‐ mediated immunotherapy; T cell; vector;

D O I：

10.1111/bph.15414

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

RNAi effectors (e.g. siRNA, shRNA and miRNA) can trigger the silencing of specific genes causing alteration of genomic functions becoming a new therapeutic area for the treatment of infectious diseases, neurodegenerative disorders and cancer. In cancer treatment, RNAi effectors showed potential immunomodulatory actions by down-regulating immuno-suppressive proteins, such as PD-1 and CTLA-4, which restrict immune cell function and present challenges in cancer immunotherapy. Therefore, compared with extracellular targeting by antibodies, RNAi-mediated cell-intrinsic disruption of inhibitory pathways in immune cells could promote an increased anti-tumour immune response. Along with non-viral vectors, DNA-based RNAi strategies might be a more promising method for immunomodulation to silence multiple inhibitory pathways in T cells than immune checkpoint blockade antibodies. Thus, in this review, we discuss diverse RNAi implementation strategies, with recent viral and non-viral mediated RNAi synergism to immunotherapy that augments the anti-tumour immunity. Finally, we provide the current progress of RNAi in clinical pipeline.

引用

页码：1741 / 1755

页数：15