mRNA肿瘤疫苗的免疫学机制和临床研究进展

Immunologic Mechanisms and Advances in Clinical Research for The mRNA Cancer Vaccine

信使核糖核酸(messenger RNA,mRNA)疗法是基于体外转录(in vitro transcription,IVT)mRNA的一种新型有效的治疗手段,在恶性肿瘤治疗领域显示了潜在的临床应用前景。21世纪之初新型冠状病毒肺炎(COVID-19)疫情的突然爆发,极大地推动了mRNA技术在严重急性呼吸综合征冠状病毒2(SARS-CoV-2)疫苗研发领域的应用。与此同时,mRNA肿瘤疫苗也成为备受瞩目的研究热点领域。通过优化和改进mRNA制备策略、mRNA疫苗递送系统、抗肿瘤免疫应答策略等,使mRNA肿瘤疫苗研发的关键技术取得了飞跃发展,加速了mRNA疗法的研究进程和临床应用,大大克服了过去mRNA疫苗面临的稳定性差、递送率低和免疫原性弱等瓶颈问题。本文综述了mRNA制备策略、mRNA疫苗递送系统、抗肿瘤免疫应答策略、mRNA疫苗治疗肿瘤的免疫学机制、不同种类mRNA肿瘤疫苗产品的临床研究进展及未来发展面临的挑战与展望等。

Messenger RNA(mRNA)therapy is a novel anticancer treatment strategy based on in vitro transcription(IVT)mRNA,with promising potential for the treatment of malignant tumors.The outbreak of the COVID-19 pandemic in the early 21st century has greatly promoted the application of mRNA technologies in SARS-CoV-2 vaccines.Meanwhile,the research and development of the mRNA cancer vaccine has become a priority.A number of key technologies,including mRNA production strategies,delivery systems,anti-tumor immune strategies,etc.,have made dramatic improvements and modifications.These technologies accelerated the research progress and clinical applications of mRNA therapy,thereby greatly overcoming the bottleneck problem,such as the instability,inefficient deliveries,and weak immunogenicity of the mRNA vaccines in the past.This review provides a detailed overview of the production,delivery systems,immunological mechanisms,and antitumor immune response strategies for mRNA cancer vaccines.We list some mRNA cancer vaccines that have been used as candidates for cancer treatment and the clinical trials in the field of tumor immunotherapy.In addition,we discuss about the immunological mechanism of the mRNA vaccines to destroy tumors,as well as the challenges and prospects for the future.