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溶瘤病毒驱动的生物疗法从实验室到临床。

Oncolytic Virus-Driven Biotherapies from Bench to Bedside.

机构信息

Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, China Medical University, Ministry of Education, Phase I Clinical Trials Center, The First Hospital of China Medical University, Shenyang, 110001, China.

Clinical Trial Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

出版信息

Small. 2023 Jun;19(23):e2206948. doi: 10.1002/smll.202206948. Epub 2023 Mar 6.

Abstract

With advances in cancer biology and an ever-deepening understanding of molecular virology, oncolytic virus (OV)-driven therapies have developed rapidly and become a promising alternative to traditional cancer therapies. In recent years, satisfactory results for oncolytic virus therapy (OVT) are achieved at both the cellular and organismal levels, and efforts are being increasingly directed toward clinical trials. Unfortunately, OVT remains ineffective in these trials, especially when performed using only a single OV reagent. In contrast, integrated approaches, such as using immunotherapy, chemotherapy, or radiotherapy, alongside OVT have demonstrated considerable efficacy. The challenges of OVT in clinical efficacy include the restricted scope of intratumoral injections and poor targeting of intravenous administration. Further optimization of OVT delivery is needed before OVs become a viable therapy for tumor treatment. In this review, the development process and antitumor mechanisms of OVs are introduced. The advances in OVT delivery routes to provide perspectives and directions for the improvement of OVT delivery are highlighted. This review also discusses the advantages and limitations of OVT monotherapy and combination therapy through the lens of recent clinical trials and aims to chart a course toward safer and more effective OVT strategies.

摘要

随着癌症生物学的进步和对分子病毒学的深入了解,溶瘤病毒(OV)驱动的治疗方法迅速发展,成为传统癌症治疗方法的一种有前途的替代方法。近年来,在细胞和机体水平上,溶瘤病毒治疗(OVT)都取得了令人满意的效果,并且越来越多的努力都在转向临床试验。不幸的是,OVT 在这些试验中仍然无效,特别是当仅使用单一 OV 试剂时。相比之下,联合治疗,如免疫疗法、化疗或放疗与 OVT 联合使用,已显示出相当大的疗效。OVT 在临床疗效方面面临的挑战包括肿瘤内注射的范围有限和静脉给药的靶向性差。在 OV 成为肿瘤治疗的可行疗法之前,还需要进一步优化 OVT 的递送。在本文中,我们介绍了 OV 的开发过程和抗肿瘤机制。突出了 OVT 传递途径的进展,为改善 OVT 传递提供了视角和方向。本文还通过最近的临床试验的角度讨论了 OVT 单药治疗和联合治疗的优缺点,并旨在为更安全、更有效的 OVT 策略制定路线。

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