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将溶瘤病毒与美国食品药品监督管理局(FDA)批准的药物制剂联合用于癌症治疗。

Combining oncolytic virus with FDA approved pharmacological agents for cancer therapy.

作者信息

Zhang Wei, Chen Clark C, Ning Jianfang

机构信息

Department of Neurosurgery, University of Minnesota Medical School , Minneapolis, MN, USA.

出版信息

Expert Opin Biol Ther. 2021 Feb;21(2):183-189. doi: 10.1080/14712598.2020.1811848. Epub 2020 Sep 14.

Abstract

INTRODUCTION

Oncolytic viruses (OVs) have been engineered to selectively replicate in cancer cells. While initially thought to exert its anti-cancer effects through direct cytolysis, it is increasingly appreciated that OVs interact with a multitude of cellular processes during its life cycle; FDA approved pharmacologic agents that modulate these cellular processes have been shown to augment the anti-neoplastic effects of OVs. Moreover, because of the release of tumor antigens as well as the innate immuno-stimulatory nature of viruses, OVs induce potent immune responses that augment the anti-tumor effects of FDA approved immunotherapies. There is mounting interest in OV as a platform for combinational anti-cancer therapy in this context.

AREAS COVERED

We will review pre-clinical and clinical data that demonstrate proof-of-principle and potential efficacy for OV-based combination therapies with FDA approved anti-cancer agents.

EXPERT OPINION

While the cytolytic activity of OV remains a key driver for its anti-neoplastic effects, understanding the virus-host interactions may afford opportunities for potential synergism with FDA approved therapeutics that target these interactions. Most intriguingly, the immune stimulatory effects of OVs renders combination with FDA approved immunotherapies more potent. While there are growing clinical trials employing such combination therapy, meaningful advances in this paradigm will require improved understanding of virus-host interactions.

摘要

引言

溶瘤病毒(OVs)已被设计成可在癌细胞中选择性复制。虽然最初认为其通过直接细胞溶解发挥抗癌作用,但人们越来越认识到,溶瘤病毒在其生命周期中会与多种细胞过程相互作用;已证明,美国食品药品监督管理局(FDA)批准的调节这些细胞过程的药物可增强溶瘤病毒的抗肿瘤作用。此外,由于肿瘤抗原的释放以及病毒固有的免疫刺激特性,溶瘤病毒可诱导强大的免疫反应,增强FDA批准的免疫疗法的抗肿瘤作用。在这种情况下,人们对溶瘤病毒作为联合抗癌治疗平台的兴趣与日俱增。

涵盖领域

我们将回顾临床前和临床数据,这些数据证明了基于溶瘤病毒与FDA批准的抗癌药物联合治疗的原理和潜在疗效。

专家观点

虽然溶瘤病毒的细胞溶解活性仍然是其抗肿瘤作用的关键驱动因素,但了解病毒与宿主的相互作用可能为与针对这些相互作用的FDA批准的治疗方法产生潜在协同作用提供机会。最引人注目的是,溶瘤病毒的免疫刺激作用使与FDA批准的免疫疗法联合使用时更有效。虽然采用这种联合治疗的临床试验越来越多,但要在这一模式上取得有意义的进展,需要更好地理解病毒与宿主的相互作用。

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