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腺病毒疗法治疗宫颈癌:从靶向修饰到免疫治疗

Adenoviral Therapy for Cervical Cancer: From Targeted Modification to Immunotherapy.

作者信息

Li Yufeng, Zhang Haibin, Xin Wenhu, Qin Tiansheng

机构信息

Department of Gynecology, The Second Hospital & Clinical Medical School, Lanzhou University , Lanzhou, 730030, China.

出版信息

Anticancer Agents Med Chem. 2025;25(14):967-977. doi: 10.2174/0118715206338559241112060553.


DOI:10.2174/0118715206338559241112060553
PMID:39871567
Abstract

Cervical cancer is a significant global health threat, ranking as the fourth most common malignancy among women and resulting in over 300,000 deaths annually. Although screening and vaccination initiatives have led to a decline in incidence rates, treatment options for advanced or recurrent cervical cancer remain inadequate, often proving ineffective and costly. In this context, adenoviral therapy has emerged as a promising strategy to enhance therapeutic outcomes. Adenoviruses are non-enveloped viruses that can efficiently infect a wide range of cells, including tumor cells, while exhibiting a favorable safety profile, making them suitable candidates for clinical applications. Adenoviral vectors possess the unique ability to package large segments of therapeutic genes, allowing for diverse treatment approaches, including oncolytic virotherapy, which selectively targets and destroys tumor cells while stimulating robust immune responses. By engineering adenoviruses to express tumor suppressor genes such as p53, researchers can restore critical apoptotic pathways often disrupted in cervical cancer. Furthermore, genetic modifications to capsid proteins can enhance the targeting of tumor cells and reduce the immunogenicity associated with these viral vectors. Additionally, adenoviral vectors can serve as delivery systems for therapeutic vaccines against HPV oncogenes E6 and E7, promoting effective immune responses and potentially preventing disease progression. The combination of adenoviral therapy with immune checkpoint inhibitors offers a novel approach to overcoming the immunosuppressive tumor microenvironment, enhancing overall antitumor immunity. Overall, this review highlights the significant advancements in adenoviral therapy for cervical cancer, emphasizing the need for further research to optimize these strategies and translate preclinical successes into effective clinical applications. By harnessing the full potential of adenoviral vectors, we can improve treatment options for patients who have cervical cancer, paving the way for more personalized and effective therapeutic interventions.

摘要

宫颈癌是全球重大的健康威胁,是女性中第四大常见恶性肿瘤,每年导致超过30万例死亡。尽管筛查和疫苗接种计划已使发病率有所下降,但晚期或复发性宫颈癌的治疗选择仍然不足,往往效果不佳且成本高昂。在这种背景下,腺病毒疗法已成为一种有望提高治疗效果的策略。腺病毒是非包膜病毒,能够有效感染包括肿瘤细胞在内的多种细胞,同时具有良好的安全性,使其成为临床应用的合适候选者。腺病毒载体具有包装大片段治疗基因的独特能力,允许采用多种治疗方法,包括溶瘤病毒疗法,该疗法可选择性地靶向并破坏肿瘤细胞,同时激发强大的免疫反应。通过对腺病毒进行工程改造以表达诸如p53等肿瘤抑制基因,研究人员可以恢复宫颈癌中经常被破坏的关键凋亡途径。此外,对衣壳蛋白进行基因改造可以增强对肿瘤细胞的靶向性,并降低与这些病毒载体相关的免疫原性。此外,腺病毒载体可作为针对人乳头瘤病毒癌基因E6和E7的治疗性疫苗的递送系统,促进有效的免疫反应并可能预防疾病进展。腺病毒疗法与免疫检查点抑制剂的联合使用提供了一种克服免疫抑制性肿瘤微环境、增强整体抗肿瘤免疫力的新方法。总体而言,本综述强调了腺病毒疗法在宫颈癌治疗方面的重大进展,强调需要进一步研究以优化这些策略,并将临床前的成功转化为有效的临床应用。通过充分发挥腺病毒载体的潜力,我们可以改善宫颈癌患者的治疗选择,为更个性化和有效的治疗干预铺平道路。

相似文献

[1]
Adenoviral Therapy for Cervical Cancer: From Targeted Modification to Immunotherapy.

Anticancer Agents Med Chem. 2025

[2]
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[6]
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[7]
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Cochrane Database Syst Rev. 2021-9-6

[8]
Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors.

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[9]
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本文引用的文献

[1]
A pseudotyped adenovirus serotype 5 vector with serotype 49 fiber knob is an effective vector for vaccine and gene therapy applications.

Mol Ther Methods Clin Dev. 2024-7-30

[2]
Harnessing adenovirus in cancer immunotherapy: evoking cellular immunity and targeting delivery in cell-specific manner.

Biomark Res. 2024-3-25

[3]
The human adenovirus PI3K-Akt activator E4orf1 is targeted by the tumor suppressor p53.

J Virol. 2024-4-16

[4]
RGD peptide in cancer targeting: Benefits, challenges, solutions, and possible integrin-RGD interactions.

Cancer Med. 2024-1

[5]
Oncolytic virus-based combination therapy in breast cancer.

Cancer Lett. 2024-3-31

[6]
A dual-functional oncolytic adenovirus ZD55-aPD-L1 scFv armed with PD-L1 inhibitor potentiates its antitumor activity.

Int Immunopharmacol. 2024-2-15

[7]
Immunotherapy that leverages HPV-specific immune responses for precancer lesions of cervical cancer.

Taiwan J Obstet Gynecol. 2024-1

[8]
Pharmacotherapy for the treatment of recurrent cervical cancer: an update of the literature.

Expert Opin Pharmacother. 2024

[9]
A Therapeutic DNA Vaccine Targeting HPV16 E7 in Combination with Anti-PD-1/PD-L1 Enhanced Tumor Regression and Cytotoxic Immune Responses.

Int J Mol Sci. 2023-10-23

[10]
Combined cytotoxic and immune-stimulatory gene therapy for primary adult high-grade glioma: a phase 1, first-in-human trial.

Lancet Oncol. 2023-9

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