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新兴的免疫疗法作为癌症抗血管生成治疗手段。

Emerging immunologic approaches as cancer anti-angiogenic therapies.

作者信息

Azimi Mohammadreza, Manavi Mahdokht Sadat, Afshinpour Maral, Khorram Roya, Vafadar Reza, Rezaei-Tazangi Fatemeh, Arabzadeh Danyal, Arabzadeh Sattar, Ebrahimi Nasim, Aref Amir Reza

机构信息

Department of Biochemistry, Medical Faculty, Saveh Branch, Islamic Azad University, Saveh, Iran.

Otolaryngology Department, Tehran University of Medical Science, Tehran, Iran.

出版信息

Clin Transl Oncol. 2025 Apr;27(4):1406-1425. doi: 10.1007/s12094-024-03667-2. Epub 2024 Sep 18.

DOI:10.1007/s12094-024-03667-2
PMID:39294514
Abstract

Targeting tumor angiogenesis, the formation of new blood vessels supporting cancer growth and spread, has been an intense focus for therapy development. However, benefits from anti-angiogenic drugs like bevacizumab have been limited by resistance stemming from activation of compensatory pathways. Recent immunotherapy advances have sparked interest in novel immunologic approaches that can induce more durable vascular pruning and overcome limitations of existing angiogenesis inhibitors. This review comprehensively examines these emerging strategies, including modulating tumor-associated macrophages, therapeutic cancer vaccines, engineered nanobodies and T cells, anti-angiogenic cytokines/chemokines, and immunomodulatory drugs like thalidomide analogs. For each approach, the molecular mechanisms, preclinical/clinical data, and potential advantages over conventional drugs are discussed. Innovative therapeutic platforms like nanoparticle delivery systems are explored. Moreover, the importance of combining agents with distinct mechanisms to prevent resistance is evaluated. As tumors hijack angiogenesis for growth, harnessing the immune system's specificity to disrupt this process represents a promising anti-cancer strategy covered by this review.

摘要

靶向肿瘤血管生成,即支持癌症生长和扩散的新血管形成,一直是治疗开发的重点。然而,像贝伐单抗这样的抗血管生成药物的疗效受到补偿途径激活所产生的耐药性的限制。最近免疫疗法的进展引发了人们对新型免疫方法的兴趣,这些方法可以诱导更持久的血管修剪,并克服现有血管生成抑制剂的局限性。这篇综述全面研究了这些新兴策略,包括调节肿瘤相关巨噬细胞、治疗性癌症疫苗、工程化纳米抗体和T细胞、抗血管生成细胞因子/趋化因子以及沙利度胺类似物等免疫调节药物。对于每种方法,都讨论了其分子机制、临床前/临床数据以及相对于传统药物的潜在优势。还探讨了纳米颗粒递送系统等创新治疗平台。此外,评估了联合使用具有不同机制的药物以预防耐药性的重要性。由于肿瘤利用血管生成来生长,利用免疫系统的特异性来破坏这一过程代表了一种有前景的抗癌策略,本综述对此进行了阐述。

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Mol Clin Oncol. 2023 Nov 28;20(1):7. doi: 10.3892/mco.2023.2705. eCollection 2024 Jan.
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A Novel bispecific T-cell engager (BiTE) targeting CD22 and CD3 has both in vitro and in vivo activity and synergizes with blinatumomab in an acute lymphoblastic leukemia (ALL) tumor model.一种新型双特异性 T 细胞衔接器(BiTE),靶向 CD22 和 CD3,具有体外和体内活性,并在急性淋巴细胞白血病(ALL)肿瘤模型中与blinatumomab 协同作用。
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Kymriah® (tisagenlecleucel) - An overview of the clinical development journey of the first approved CAR-T therapy.
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Hum Vaccin Immunother. 2023 Dec 31;19(1):2210046. doi: 10.1080/21645515.2023.2210046. Epub 2023 May 15.
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Disrupting cancer angiogenesis and immune checkpoint networks for improved tumor immunity.破坏癌症血管生成和免疫检查点网络以增强肿瘤免疫。
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The Role of the IL-23/IL-17 Axis in Disease Initiation in Spondyloarthritis: Lessons Learned From Animal Models.IL-23/IL-17 轴在脊柱关节炎发病中的作用:从动物模型中得到的启示。
Front Immunol. 2021 Jun 29;12:618581. doi: 10.3389/fimmu.2021.618581. eCollection 2021.
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