Suppr超能文献

溶瘤病毒与免疫检查点抑制剂:从临床前研发到临床试验

Oncolytic Viruses and Immune Checkpoint Inhibitors: Preclinical Developments to Clinical Trials.

机构信息

Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea.

GeneMedicine Co., Ltd., 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea.

出版信息

Int J Mol Sci. 2020 Nov 16;21(22):8627. doi: 10.3390/ijms21228627.

Abstract

Immuno-oncology (IO) has been an active area of oncology research. Following US FDA approval of the first immune checkpoint inhibitor (ICI), ipilimumab (human IgG1 k anti-CTLA-4 monoclonal antibody), in 2011, and of the first oncolytic virus, Imlygic (talimogene laherparepvec), in 2015, there has been renewed interest in IO. In the past decade, ICIs have changed the treatment paradigm for many cancers by enabling better therapeutic control, resuming immune surveillance, suppressing tumor immunosuppression, and restoring antitumor immune function. However, ICI therapies are effective only in a small subset of patients and show limited therapeutic potential due to their inability to demonstrate efficacy in 'cold' or unresponsive tumor microenvironments (TMEs). Relatedly, oncolytic viruses (OVs) have been shown to induce antitumor immune responses, augment the efficacy of existing cancer treatments, and reform unresponsive TME to turn 'cold' tumors 'hot,' increasing their susceptibility to checkpoint blockade immunotherapies. For this reason, OVs serve as ideal complements to ICIs, and multiple preclinical studies and clinical trials are demonstrating their combined therapeutic efficacy. This review will discuss the merits and limitations of OVs and ICIs as monotherapy then progress onto the preclinical rationale and the results of clinical trials of key combination therapies.

摘要

免疫肿瘤学(IO)一直是肿瘤学研究的活跃领域。继 2011 年美国食品和药物管理局(FDA)批准首个免疫检查点抑制剂(ICI)——伊匹单抗(抗 CTLA-4 人源 IgG1k 单克隆抗体),以及 2015 年批准首个溶瘤病毒——替莫唑胺(talimogene laherparepvec)之后,IO 领域又重新引起了人们的兴趣。在过去的十年中,ICI 通过更好的治疗控制、恢复免疫监测、抑制肿瘤免疫抑制和恢复抗肿瘤免疫功能,改变了许多癌症的治疗模式。然而,由于其在“冷”或无反应性肿瘤微环境(TME)中无法显示疗效,ICI 疗法仅对一小部分患者有效,且显示出有限的治疗潜力。相关地,溶瘤病毒(OVs)已被证明可诱导抗肿瘤免疫反应,增强现有癌症治疗的疗效,并重塑无反应性 TME,使“冷”肿瘤“热”化,增加其对检查点阻断免疫疗法的敏感性。出于这个原因,OVs 是 ICI 的理想补充,并且多项临床前研究和临床试验正在证明它们的联合治疗疗效。这篇综述将讨论 OVs 和 ICI 作为单一疗法的优缺点,然后探讨关键联合疗法的临床前原理和临床试验结果。

相似文献

1
Oncolytic Viruses and Immune Checkpoint Inhibitors: Preclinical Developments to Clinical Trials.
Int J Mol Sci. 2020 Nov 16;21(22):8627. doi: 10.3390/ijms21228627.
2
Oncolytic Viruses: Priming Time for Cancer Immunotherapy.
BioDrugs. 2019 Oct;33(5):485-501. doi: 10.1007/s40259-019-00367-0.
3
Oncolytic Viruses in Cancer Treatment: A Review.
JAMA Oncol. 2017 Jun 1;3(6):841-849. doi: 10.1001/jamaoncol.2016.2064.
4
Phase I study of VSV-GP (BI 1831169) as monotherapy or combined with ezabenlimab in advanced and refractory solid tumors.
Future Oncol. 2022 Aug;18(24):2627-2638. doi: 10.2217/fon-2022-0439. Epub 2022 Jun 14.
5
Combination therapy with oncolytic viruses and immune checkpoint inhibitors.
Expert Opin Biol Ther. 2020 Jun;20(6):635-652. doi: 10.1080/14712598.2020.1729351. Epub 2020 Feb 23.
6
Oncolytic virotherapy in cancer treatment: challenges and optimization prospects.
Front Immunol. 2023 Dec 15;14:1308890. doi: 10.3389/fimmu.2023.1308890. eCollection 2023.
7
Oncolytic viruses combined with immune checkpoint therapy for colorectal cancer is a promising treatment option.
Front Immunol. 2022 Jul 15;13:961796. doi: 10.3389/fimmu.2022.961796. eCollection 2022.
9
Fueling immune checkpoint blockade with oncolytic viruses: Current paradigms and challenges ahead.
Cancer Lett. 2022 Dec 1;550:215937. doi: 10.1016/j.canlet.2022.215937. Epub 2022 Oct 4.
10
New hopes for the breast cancer treatment: perspectives on the oncolytic virus therapy.
Front Immunol. 2024 Mar 21;15:1375433. doi: 10.3389/fimmu.2024.1375433. eCollection 2024.

引用本文的文献

1
Recent advances in oncolytic virus combined immunotherapy in tumor treatment.
Genes Dis. 2025 Mar 12;12(6):101599. doi: 10.1016/j.gendis.2025.101599. eCollection 2025 Nov.
2
Therapeutic Colorectal Cancer Vaccines: Emerging Modalities and Translational Opportunities.
Vaccines (Basel). 2025 Jun 26;13(7):689. doi: 10.3390/vaccines13070689.
3
Cell Carriers for Oncolytic Virus Delivery: Prospects for Systemic Administration.
Cancers (Basel). 2025 Jul 10;17(14):2296. doi: 10.3390/cancers17142296.
4
Advances in Gene Therapy with Oncolytic Viruses and CAR-T Cells and Therapy-Related Groups.
Curr Issues Mol Biol. 2025 Apr 10;47(4):268. doi: 10.3390/cimb47040268.
5
Advances in Genitourinary Tumor Genomics and Immunotherapy.
Genes (Basel). 2025 May 30;16(6):667. doi: 10.3390/genes16060667.
7
Extracellular matrix re-normalization to improve cold tumor penetration by oncolytic viruses.
Front Immunol. 2025 Jan 8;15:1535647. doi: 10.3389/fimmu.2024.1535647. eCollection 2024.
8
Antibiotic-mediated selection of randomly mutagenized and cytokine-expressing oncolytic viruses.
Nat Biomed Eng. 2025 Jun;9(6):822-835. doi: 10.1038/s41551-024-01259-7. Epub 2024 Nov 28.
9
Immunotherapy for colorectal cancer.
Front Immunol. 2024 Aug 21;15:1433315. doi: 10.3389/fimmu.2024.1433315. eCollection 2024.
10
Where Are We Now with Oncolytic Viruses in Melanoma and Nonmelanoma Skin Malignancies?
Pharmaceuticals (Basel). 2024 Jul 9;17(7):916. doi: 10.3390/ph17070916.

本文引用的文献

2
Overcoming the limitations of locally administered oncolytic virotherapy.
BMC Biomed Eng. 2019 Jul 1;1:17. doi: 10.1186/s42490-019-0016-x. eCollection 2019.
3
Metabolic Modulation of Immunity: A New Concept in Cancer Immunotherapy.
Cell Rep. 2020 Jul 7;32(1):107848. doi: 10.1016/j.celrep.2020.107848.
4
Oncolytic viruses for cancer immunotherapy.
J Hematol Oncol. 2020 Jun 29;13(1):84. doi: 10.1186/s13045-020-00922-1.
6
Repurposing infectious disease vaccines for intratumoral immunotherapy.
J Immunother Cancer. 2020 Feb;8(1). doi: 10.1136/jitc-2019-000443.
7
Combination therapy with oncolytic viruses and immune checkpoint inhibitors.
Expert Opin Biol Ther. 2020 Jun;20(6):635-652. doi: 10.1080/14712598.2020.1729351. Epub 2020 Feb 23.
8
Toxicities associated with checkpoint inhibitors-an overview.
Rheumatology (Oxford). 2019 Dec 1;58(Suppl 7):vii7-vii16. doi: 10.1093/rheumatology/kez418.
9
Immuno-oncology drug development goes global.
Nat Rev Drug Discov. 2019 Nov;18(12):899-900. doi: 10.1038/d41573-019-00167-9.
10
Preclinical And Clinical Development Of Oncolytic Adenovirus For The Treatment Of Malignant Glioma.
Oncolytic Virother. 2019 Oct 24;8:27-37. doi: 10.2147/OV.S196403. eCollection 2019.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验