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优化恶性胶质瘤的溶瘤病毒疗法:从 bench 到 bedside

Optimizing Oncolytic Virotherapy for Malignant Glioma: From Bench to Bedside.

作者信息

Jiang Weihua, Tian Yeqing, Gu Huafen, Guan Wenqing

机构信息

Department of Neurology, First People's Hospital of Linping District, Hangzhou, People's Republic of China.

The Radiology Department of The First People's Hospital of Linping District, Hangzhou, People's Republic of China.

出版信息

Cancer Manag Res. 2025 Aug 4;17:1537-1554. doi: 10.2147/CMAR.S528875. eCollection 2025.


DOI:10.2147/CMAR.S528875
PMID:40786912
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12333633/
Abstract

Malignant glioma is a highly aggressive brain tumor characterized by frequent recurrence, poor prognosis, and limited responsiveness to standard therapies. Glioblastoma multiforme, the most common and aggressive subtype, further complicates treatment due to its infiltrative nature, genetic heterogeneity, the protective blood-brain barrier, and an immunosuppressive microenvironment. Despite aggressive treatment strategies such as surgical resection combined with chemoradiotherapy, the median survival for malignant glioma patients remains low, highlighting the urgent need for more effective therapeutic approaches. Oncolytic virotherapy (OVT), a dual-modality approach that combines immunotherapy and biotherapy, has emerged as a promising alternative. Oncolytic viruses (OVs) can replicate continuously, disseminate within the tumor, and stimulate anti-tumor immunity, offering distinct advantages in targeting invasive and immunologically "cold" malignant glioma. However, the efficacy of OVT in clinical trials remains unsatisfactory, particularly in single-agent regimens. This limitation is primarily attributed to the viruses' limited replication efficiency, suboptimal immune induction, premature clearance by antiviral immune responses, and the blood-brain barrier, which impedes effective intracranial delivery. Thus, further optimization of viral modifications, delivery systems, and treatment regimens is critical to enhancing therapeutic potency before OVT can become a standard therapy for malignant glioma. This review systematically summarizes current strategies for enhancing OVs, including genetic engineering, chemical functionalization, and carrier-based delivery. Furthermore, it highlights combination therapies that aim to synergistically enhance therapeutic efficacy through chemotherapy, radiotherapy, and immunotherapy. Finally, the review emphasizes recent clinical trials leveraging these enhancement strategies, aiming to offer novel insights for translating OVs from research to clinical practice.

摘要

恶性胶质瘤是一种侵袭性很强的脑肿瘤,其特点是频繁复发、预后不良,对标准治疗的反应有限。多形性胶质母细胞瘤是最常见且侵袭性最强的亚型,由于其浸润性、基因异质性、保护性血脑屏障以及免疫抑制微环境,使治疗更加复杂。尽管采取了积极的治疗策略,如手术切除联合放化疗,但恶性胶质瘤患者的中位生存期仍然很低,这凸显了对更有效治疗方法的迫切需求。溶瘤病毒疗法(OVT)是一种将免疫疗法和生物疗法相结合的双模式方法,已成为一种有前景的替代疗法。溶瘤病毒(OVs)可以持续复制,在肿瘤内扩散,并刺激抗肿瘤免疫,在靶向侵袭性和免疫“冷”性恶性胶质瘤方面具有独特优势。然而,OVT在临床试验中的疗效仍然不尽人意,尤其是在单药治疗方案中。这一局限性主要归因于病毒的复制效率有限、免疫诱导效果欠佳、抗病毒免疫反应导致的过早清除以及血脑屏障,后者阻碍了有效的颅内递送。因此,在OVT成为恶性胶质瘤的标准治疗方法之前,进一步优化病毒修饰、递送系统和治疗方案对于提高治疗效果至关重要。本综述系统总结了目前增强OVs的策略,包括基因工程、化学功能化和基于载体的递送。此外,还强调了旨在通过化疗、放疗和免疫疗法协同提高治疗效果的联合疗法。最后,本综述强调了利用这些增强策略的近期临床试验,旨在为将OVs从研究转化为临床实践提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/543d/12333633/93a134df0a9e/CMAR-17-1537-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/543d/12333633/4146bc1ba066/CMAR-17-1537-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/543d/12333633/807460ef6584/CMAR-17-1537-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/543d/12333633/e4d3d51bee50/CMAR-17-1537-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/543d/12333633/58a7f4a0862e/CMAR-17-1537-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/543d/12333633/93a134df0a9e/CMAR-17-1537-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/543d/12333633/4146bc1ba066/CMAR-17-1537-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/543d/12333633/807460ef6584/CMAR-17-1537-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/543d/12333633/e4d3d51bee50/CMAR-17-1537-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/543d/12333633/58a7f4a0862e/CMAR-17-1537-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/543d/12333633/93a134df0a9e/CMAR-17-1537-g0005.jpg

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本文引用的文献

[1]
Engineered oncolytic virus coated with anti-PD-1 and alendronate for ameliorating intratumoral T cell hypofunction.

Exp Hematol Oncol. 2025-2-15

[2]
Overexpression of miR-124 enhances the therapeutic benefit of TMZ treatment in the orthotopic GBM mice model by inhibition of DNA damage repair.

Cell Death Dis. 2025-1-26

[3]
Extracellular matrix re-normalization to improve cold tumor penetration by oncolytic viruses.

Front Immunol. 2025-1-8

[4]
Improving systemic delivery of oncolytic virus by cellular carriers.

Cancer Biol Med. 2025-1-17

[5]
Oncolytic Virus Targeted Therapy for Glioma via Intravenous Delivery.

Adv Healthc Mater. 2025-3

[6]
Anti-PD-1 and anti-PD-L1 antibodies for glioma.

Cochrane Database Syst Rev. 2025-1-8

[7]
Viral-Porphyrin Combo: Photodynamic and Oncolytic Viral Therapy for Potent Glioblastoma Treatment.

Int J Mol Sci. 2024-11-22

[8]
Non-secreting IL12 expressing oncolytic adenovirus Ad-TD-nsIL12 in recurrent high-grade glioma: a phase I trial.

Nat Commun. 2024-11-8

[9]
Recent advances in spatio-temporally controllable systems for management of glioma.

Asian J Pharm Sci. 2024-10

[10]
Adipose-Derived Stem Cells as Carrier of Pro-Apoptotic Oncolytic Myxoma Virus: To Cross the Blood-Brain Barrier and Treat Murine Glioma.

Int J Mol Sci. 2024-10-18

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