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基于寄生虫的癌症生物治疗策略及临床前应用

英文原题:Parasite based biotherapy for cancer therapeutic strategies and preclinical applications.

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Parasite based biotherapy for cancer therapeutic strategies and preclinical applications.

PubMed 2026/06/13(内容时间) Discov Oncol Q3 · IF 2.8(JCR 2025)

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研究概要

基于寄生虫的生物治疗在肿瘤免疫治疗中代表了一种生物学上具有吸引力但实验上受限的方法。其临床转化受到生物安全问题、寄生虫生命周期复杂性、宿主-寄生虫相互作用的异质性以及缺乏标准化递送平台的限制。未来工作应聚焦于机制解析、严格的安全性评估,以及与免疫检查点阻断和其他已确立的免疫治疗的合理整合,以实现有意义的临床进展。

研究思路结论见上方概要

癌症免疫治疗通过使多种恶性肿瘤获得持久缓解而改变了肿瘤学格局;然而,其临床疗效仍受限于免疫逃逸、治疗耐药和治疗相关毒性。在此背景下,寄生虫——长期以来被视为病原体——已成为情境依赖性的免疫调节系统,能够以有益和有害两个方向重塑宿主免疫。主要内容:本小型综述批判性整合了基于寄生虫的癌症生物治疗的临床前证据,重点关注原虫(Plasmodium spp.、Toxoplasma gondii、Leishmania spp.)和部分蠕虫(Trichinella spiralis、Echinococcus granulosus)。我们强调其双重生物学作用:虽然某些寄生虫感染在实验模型中表现出抗肿瘤活性,但其他寄生虫感染通过慢性炎症、纤维化、氧化应激和基因组不稳定性与癌发生密切相关。已报道的抗肿瘤机制包括激活细胞毒性T淋巴细胞和NK细胞、调节Th1/Th2免疫平衡、抑制血管生成和上皮-间质转化、诱导凋亡以及重编程肿瘤微环境。与此同时,寄生虫来源成分如排泄-分泌产物、抗原蛋白和细胞外囊泡在小鼠癌症模型中显示出一致的免疫调节作用。值得注意的是,当前证据基础在很大程度上仍局限于临床前系统,仅有有限的早期转化探索。

展开英文摘要原文

Cancer immunotherapy has transformed oncology by enabling durable responses in multiple malignancies; however, its clinical efficacy remains limited by immune evasion, therapeutic resistance, and treatment-related toxicity. In this context, parasites-long considered pathogenic organisms-have emerged as context-dependent immunomodulatory systems capable of reshaping host immunity in both beneficial and detrimental directions. MAIN BODY: This mini-review critically synthesizes preclinical evidence on parasite-based cancer biotherapy, focusing on protozoa (Plasmodium spp., Toxoplasma gondii, Leishmania spp.) and selected helminths (Trichinella spiralis, Echinococcus granulosus). We emphasize their dual biological role: while certain parasitic infections demonstrate antitumor activity in experimental models, others are strongly implicated in carcinogenesis through chronic inflammation, fibrosis, oxidative stress, and genomic instability. Reported antitumor mechanisms include activation of cytotoxic T lymphocytes and NK cells, modulation of Th1/Th2 immune balance, inhibition of angiogenesis and epithelial-mesenchymal transition, induction of apoptosis, and reprogramming of the tumor microenvironment. In parallel, parasite-derived components such as excretory-secretory products, antigenic proteins, and extracellular vesicles have shown consistent immunomodulatory effects in murine cancer models. Notably, the current evidence base remains largely restricted to preclinical systems, with only limited early translational exploration.

Parasite-based biotherapy represents a biologically compelling yet experimentally constrained approach in cancer immunotherapy. Its clinical translation is limited by biosafety concerns, parasite lifecycle complexity, heterogeneity of host-parasite interactions, and lack of standardized delivery platforms. Future work should focus on mechanistic dissection, rigorous safety evaluation, and rational integration with immune checkpoint blockade and other established immunotherapies to enable meaningful clinical advancement.

论文信息

作者
Mehdioghli R、Chavshin A、Bakhshipour F、Hanifian H
第一作者单位
Palliative Care Research Center, U.R.C. Islamic Azad University, Urmia, Iran.Iran
通讯作者单位
Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. h-hanifian@tums.ac.ir.Iran
文献类型
综述
期刊
Discover oncology2026 Jun 13
原文标识
PubMed 42288711 · DOI 10.1007/s12672-026-05444-9