摘要
新型冠状病毒感染(corona virus disease 2019,COVID-19)mRNA疫苗成功研制,使得mRNA疫苗和药物成为癌症免疫治疗的一个有前途的平台。mRNA癌症疫苗和药物具有高效、安全、开发快速和经济成本低等优势。研究人员对mRNA疫苗的组成成分和递送载体进行了系统性优化,克服了其稳定性差、具有固有免疫原性和体内递送效率低等问题,使COVID-19 mRNA疫苗获批临床应用。尽管还没有mRNA癌症疫苗和药物获批临床应用,但是编码肿瘤抗原、治疗性抗体、细胞因子、肿瘤抑制因子、溶瘤病毒、CRISPR-Cas9、嵌合抗原受体(CAR)、T细胞受体(TCR)mRNA癌症疫苗和药物已经在临床前研究中显示出疗效,并且有一些已经进入临床试验。同时mRNA癌症疫苗和药物与检查点抑制剂联合应用,在临床试验中已取得显著有效的成果。本文对mRNA疫苗和药物的免疫机制、分类、修饰方法、递送系统、多种癌症疫苗和药物的临床应用现状和该领域当前挑战以及未来前景进行了综述,并期待mRNA癌症疫苗和药物尽快的应用于临床,使患者受益。
mRNA vaccines and drugs enter host cells through delivery vectors and produce target proteins using the protein synthesis mechanism of cells.mRNA and target proteins can induce the body to produce innate immunity and adaptive immunity,and the target protein itself can also play a corresponding role.Tumor cells are inhibited and cleared under the above immune effects and target proteins.This article reviews the immunogenicity of mRNA,that is,the specific mechanism of stimulating the body to produce an immune response.At the same time,the main types of cells transfected by mRNA vaccine were briefly introduced.(1)Muscle cells,epidermal cells,dendritic cells and macrophages at the injection site;(2)immune cells in peripheral lymphoid organs;(3)liver cells and spleen cells,etc.Although transfected with a variety of cells,it is mainly enriched in immune cells and liver cells because immune cells express toll-like receptors and liver cells express low-density lipoprotein receptors.mRNA vaccines and drugs are mainly divided into non-replicating mRNA(nrmRNA),self-amplifying RNA(saRNA),trans-amplifying RNA(taRNA)and circular RNA(circRNA).This article reviews how these 4 types of vaccines and drugs work,and compares their advantages and disadvantages.Due to its inherent immunogenicity,instability,and low delivery efficiency in vivo,mRNA vaccines and drugs have been unable to enter the clinic.This article describes in detail how to reformation and modify the 5'cap,5'UTR,3'UTR,ORF,3'Poly(A)and some nucleotides of mRNA to eliminate its immunogenicity and instability.Due to the low efficiency of the delivery carrier,the researchers optimized it.This article briefly introduces the application of non viral vectors and their targeting,specifically involving the mechanism of action of various types of delivery vectors and their advantages and disadvantages,and summarizes some of the current targeting vectors.Targeted carriers can improve the delivery efficiency of mRNA to specific tissues and prevent side effects of systemic exposu
作者
未志盟
党生
李光晨
高兰柱
翟景波
WEI Zhi-Meng;DANG Sheng;LI Guang-Chen;GAO Lan-Zhu;ZHAI Jing-Bo(Medical College,Inner Mongolia Minzu University,Tongliao 028000,China;Department of Laboratory,Department of Pathology,Keerqin District First People’s Hospital,Tongliao 028000,China;Infectious Diseases Department,Tongliao Infectious Disease Hospital,Tongliao 028000,China;Key Laboratory of Zoonose Prevention and Control at Universities of Inner Mongolia Autonomous Region,Tongliao 028000,China;Brucellosis Prevention and Treatment Engineering Research Center of Inner Mongolia Autonomous Region,Tongliao 028000,China)
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2024年第9期2115-2132,共18页
Progress In Biochemistry and Biophysics
基金
国家自然科学基金(82160312)
内蒙古自治区自然科学基金(2023MS08057)
内蒙古教育厅人兽共患病防控自治区高等学校重点实验室开放课题(MDK2023015,MDK2023017,MDK2023018)资助项目。
关键词
mRNA癌症疫苗和药物
免疫机制
分类
修饰方法
递送系统
临床应用
mRNA cancer vaccines and drugs
immune mechanism
classification
modification methods
delivery systems
clinical application
