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膀胱癌药物卡介苗细胞壁骨架:聚焦局限性的替代方案与进展

Bladder Cancer Medication Bacillus Calmette-Guérin-Cell Wall Skeleton Focusing on Alternatives and Developments to Limitations.

作者信息

Lee Hyejin, Jang Hyerim, Kim Jeongyeon, Maeng Seoyeon, Kim Jihye

机构信息

Department of Biopharmaceutical Engineering, Hannam University, Daejeon, Korea.

出版信息

J Cancer Prev. 2025 Mar 30;30(1):1-6. doi: 10.15430/JCP.25.002.

DOI:10.15430/JCP.25.002
PMID:40201027
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11973459/
Abstract

Bacillus Calmette-Guérin (BCG) serves as an anticancer drug for bladder cancer by enhancing the innate immune response and facilitating the expression of beta-defensin-2/-3. BCG is significantly more effective than other treatment modalities; however, it has limitations due to the nonspecific secretion of immune proteins such as interleukin-2 (IL-2) and IFN-γ, necessitating frequent injections that result in toxicity. The newly developed BCG-cell wall skeleton (BCG-CWS) is intended to address the non-specificity and the requirement for repeated treatments associated with BCG. BCG-CWS stimulates antigen-presenting cells by secreting cytokines such as IL-12, using an adjuvant to enhance the immune response and synergize with it to provoke a potent immune reaction. Nevertheless, BCG-CWS encounters issues related to cellular uptake due to the substantial molecular weight of the drug. To meet this challenge, various strategies such as the introduction of R8 protein, the liposome evaporated via an emulsified lipid method, and nanoparticle formulation have been employed which can enhance targeted drug delivery, though issues related to particle size remain unresolved. This paper aims to discuss future perspectives by examining the mechanisms and challenges of BCG-CWS.

摘要

卡介苗(BCG)通过增强先天免疫反应和促进β-防御素-2/-3的表达,作为膀胱癌的抗癌药物。卡介苗比其他治疗方式显著更有效;然而,由于免疫蛋白如白细胞介素-2(IL-2)和干扰素-γ的非特异性分泌,它存在局限性,需要频繁注射,这会导致毒性。新开发的卡介苗细胞壁骨架(BCG-CWS)旨在解决与卡介苗相关的非特异性和重复治疗需求问题。BCG-CWS通过分泌如IL-12等细胞因子来刺激抗原呈递细胞,使用佐剂增强免疫反应并与之协同作用以引发强烈的免疫反应。然而,由于药物分子量较大,BCG-CWS存在与细胞摄取相关的问题。为应对这一挑战,已采用了各种策略,如引入R8蛋白、通过乳化脂质法蒸发的脂质体以及纳米颗粒制剂,这些策略可以增强靶向药物递送,尽管与粒径相关的问题仍未解决。本文旨在通过研究BCG-CWS的机制和挑战来探讨未来前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6db0/11973459/67de398d8ddb/jcp-30-1-1-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6db0/11973459/b5d7d3c25fab/jcp-30-1-1-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6db0/11973459/67de398d8ddb/jcp-30-1-1-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6db0/11973459/b5d7d3c25fab/jcp-30-1-1-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6db0/11973459/67de398d8ddb/jcp-30-1-1-f2.jpg

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本文引用的文献

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World J Urol. 2025 Jan 3;43(1):57. doi: 10.1007/s00345-024-05392-5.
2
Chemoresistance-motility signature of molecular evolution to chemotherapy in non-muscle-invasive bladder cancer and its clinical implications.非肌层浸润性膀胱癌化疗分子进化的化疗耐药-迁移特征及其临床意义。
Cancer Lett. 2025 Feb 1;610:217339. doi: 10.1016/j.canlet.2024.217339. Epub 2024 Nov 26.
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Intranasal immunization with poly I:C and CpG ODN adjuvants enhances the protective efficacy against Helicobacter pylori infection in mice.
用聚肌胞苷酸(poly I:C)和CpG寡脱氧核苷酸(ODN)佐剂进行鼻内免疫可增强小鼠对幽门螺杆菌感染的保护效力。
Microbes Infect. 2025 Mar-Apr;27(3):105433. doi: 10.1016/j.micinf.2024.105433. Epub 2024 Oct 24.
4
Liposome-Encapsulated Bacillus Calmette-Guérin Cell Wall Skeleton Enhances Antitumor Efficiency for Bladder Cancer In Vitro and In Vivo via Induction of AMP-Activated Protein Kinase.脂质体包裹的卡介苗细胞壁骨架通过诱导AMP激活的蛋白激酶增强膀胱癌的体内外抗肿瘤效率。
Cancers (Basel). 2020 Dec 8;12(12):3679. doi: 10.3390/cancers12123679.
5
Side Effects of Intravesical BCG and Chemotherapy for Bladder Cancer: What They Are and How to Manage Them.膀胱癌膀胱内卡介苗和化疗的副作用:它们是什么以及如何处理。
Urology. 2021 Mar;149:11-20. doi: 10.1016/j.urology.2020.10.039. Epub 2020 Nov 10.
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Distribution of BCG-CWS-Loaded Nanoparticles in the Spleen After Intravenous Injection Affects Cytotoxic T Lymphocyte Activity.静脉注射后 BCG-CWS 纳米颗粒在脾脏中的分布影响细胞毒性 T 淋巴细胞的活性。
J Pharm Sci. 2020 Jun;109(6):1943-1950. doi: 10.1016/j.xphs.2020.02.007. Epub 2020 Feb 15.
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