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PVX和聚乙二醇化PVX作为瘤内免疫疗法的疗效。

Efficacy of PVX and PEGylated PVX as intratumoral immunotherapy.

作者信息

Ma Yifeng, Gorman Mary G, Schuphan Juliane, Steinmetz Nicole F

机构信息

Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego La Jolla CA 92093 USA

Shu and K.C. Chien and Peter Farrell Collaboratory, University of California San Diego La Jolla CA 92093 USA.

出版信息

Mater Adv. 2025 Aug 14. doi: 10.1039/d5ma00215j.

DOI:10.1039/d5ma00215j
PMID:40822669
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12352741/
Abstract

Intratumoral immunotherapy harnesses the tumor microenvironment to enhance local immune activation and systemic antitumor responses. Plant virus nanoparticles have emerged as potent immunostimulatory agents for this strategy. Here, we investigate the efficacy of PEGylated potato virus X (PVX-PEG) in a B-cell lymphoma model. We synthesized PVX-PEG using bis-PEG -NHS esters and confirmed successful conjugation through SDS-PAGE, dynamic light scattering, and transmission electron microscopy. PEGylation improved formulation stability, as evidenced by increased thermal resistance and reduced aggregation in biological conditions. , PVX-PEG exhibited prolonged tumor retention and maintained its immunotherapeutic efficacy, comparable to native PVX. Furthermore, antibody recognition of PVX-PEG was significantly reduced, highlighting its potential for clinical translation. These results suggest that PVX-PEG retains the immunostimulatory benefits of PVX while overcoming key formulation and immunogenicity challenges, supporting its advancement as a novel intratumoral immunotherapy for lymphoma.

摘要

瘤内免疫疗法利用肿瘤微环境来增强局部免疫激活和全身抗肿瘤反应。植物病毒纳米颗粒已成为该策略中强大的免疫刺激剂。在此,我们研究了聚乙二醇化马铃薯X病毒(PVX-PEG)在B细胞淋巴瘤模型中的疗效。我们使用双-PEG-NHS酯合成了PVX-PEG,并通过SDS-PAGE、动态光散射和透射电子显微镜证实了成功偶联。聚乙二醇化提高了制剂稳定性,热稳定性增加以及在生物学条件下聚集减少证明了这一点。此外,PVX-PEG表现出延长的肿瘤滞留时间,并保持其免疫治疗效果,与天然PVX相当。此外,PVX-PEG的抗体识别显著降低,突出了其临床转化潜力。这些结果表明,PVX-PEG保留了PVX的免疫刺激益处,同时克服了关键的制剂和免疫原性挑战,支持其作为淋巴瘤新型瘤内免疫疗法的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d80/12352741/b2b1140fab66/d5ma00215j-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d80/12352741/5c06f3e3c991/d5ma00215j-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d80/12352741/28508d6c2004/d5ma00215j-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d80/12352741/b2b1140fab66/d5ma00215j-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d80/12352741/5c06f3e3c991/d5ma00215j-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d80/12352741/28508d6c2004/d5ma00215j-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d80/12352741/b2b1140fab66/d5ma00215j-f3.jpg

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本文引用的文献

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Plant Virus Intratumoral Immunotherapy with CPMV and PVX Elicits Durable Antitumor Immunity in a Mouse Model of Diffuse Large B-Cell Lymphoma.利用豇豆花叶病毒(CPMV)和马铃薯X病毒(PVX)进行的植物病毒瘤内免疫疗法在弥漫性大B细胞淋巴瘤小鼠模型中引发持久抗肿瘤免疫。
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Virus-like Particles Armored by an Endoskeleton.
被内骨骼武装的病毒样颗粒
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Immunotherapeutic Agents for Intratumoral Immunotherapy.用于瘤内免疫治疗的免疫治疗药物。
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Intratumoral Immunotherapy: Is It Ready for Prime Time?瘤内免疫疗法:它准备好进入黄金时代了吗?
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