溶瘤病毒递送策略的研究进展

Research progress on oncolytic virus delivery strategies

溶瘤病毒(Oncolytic virus,OV)能够特异性地在肿瘤细胞内复制并造成肿瘤细胞裂解,而对正常细胞无影响,因此被视为对免疫检查点抑制剂治疗后无反应或未能实现持久反应的癌症患者的一种治疗选择。目前多款溶瘤病毒疗法陆续获批上市。局部瘤内注射溶瘤病毒是目前主流疗法,然而该疗法对转移性癌症患者疗效有限。近年来,全身静脉递送溶瘤病毒疗法逐渐兴起。这种疗法的递送方式包括细胞运输、基因和纳米修饰、聚合物涂层、非生物载体、与免疫抑制剂联合等,可以协助溶瘤病毒逃避机体免疫或引发机体抗肿瘤免疫,以提高溶瘤病毒的递送和治疗效率。本综述对溶瘤病毒用药方式、给药与效应屏障、溶瘤病毒递送策略进行总结。

An oncolytic virus(OV)represents a potential therapeutic option for cancer patients who do not respond or fail to achieve a durable response to immune checkpoint inhibitor therapy.This is due to the OV's capacity to replicate specifically in tumour cells,thereby causing tumour cell lysis without affecting normal cells.A number of oncolytic virotherapies are currently undergoing the approval process and are being marketed.The current mainstay of therapy is the local intratumoural injection of oncolytic viruses(OVs).Nevertheless,this strategy has demonstrated limited efficacy in patients with metastatic cancer.In recent years,there has been a growing interest in the use of systemic intravenous delivery of OVs as a potential therapeutic approach.Delivery modalities for this therapy include cellular transport,genetic and nano-modifications,polymer coatings,abiotic vectors,and combinations with immunosuppressive agents,which can assist OVs in evading the body's immunity or triggering the body's anti-tumour immunity in order to improve OVs delivery and therapeutic efficacy.This review provides a summary of OVs dosing modalities,administration and effect barriers,and OVs delivery strategies.