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噬菌体MX1病毒样颗粒的NHAcGD2/NHAcGD3缀合物作为抗癌疫苗的研发。

Development of NHAcGD2/NHAcGD3 conjugates of bacteriophage MX1 virus-like particles as anticancer vaccines.

作者信息

Zhao Qingyu, Huang Xuefei, Wu Xuanjun

机构信息

National Glycoengineering Research Center and Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-based Medicine, Shandong University Qingdao Shandong 266237 China

Departments of Chemistry and Biomedical Engineering, Institute for Quantitative Health Science and Engineering, Michigan State University East Lansing Michigan 48824 USA.

出版信息

RSC Adv. 2024 Feb 19;14(9):6246-6252. doi: 10.1039/d3ra08923a. eCollection 2024 Feb 14.

DOI:10.1039/d3ra08923a
PMID:38375005
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10875654/
Abstract

The successful development of an anticancer vaccine will be a giant leap forward in cancer prevention and treatment. Herein, the bacteriophage MX1 coat protein virus-like particles (MX1 VLPs) have been conjugated with 9NHAc-GD2 (NHAcGD2) to obtain a MX1-NHAcGD2 conjugate. Intriguingly, vaccinating against this conjugate produced a robust anti-NHAcGD2 IgG response in mice, with an average IgG titer of over 3 million. More interestingly, antibodies induced by the MX1-NHAcGD2 conjugate bound well to IMR-32 neuroblastoma cells and had potent complement-dependent cytotoxic (CDC) effects on IMR-32 cells. Inspired by the superiority of the 9NHAc-GD2 antigen, we also designed another 9NHAc-modified ganglioside antigen, 9NHAc-GD3 (NHAcGD3), to overcome the hydrolytic instability of 9--acetylated-GD3. By coupling NHAcGD3 with MX1 VLP, the MX1-NHAcGD3 conjugate was constructed. Strikingly, vaccination of MX1-NHAcGD3 elicited high anti-NHAcGD3 IgG antibodies, which effectively recognized human malignant melanoma SK-MEL-28 cells and had a significant CDC effect against this cell line. This study provides novel MX1-NHAcGD2 and MX1-NHAcGD3 conjugates with broad clinical translational prospects as promising anticancer vaccines.

摘要

抗癌疫苗的成功研发将是癌症预防和治疗领域向前迈出的巨大一步。在此，噬菌体MX1外壳蛋白病毒样颗粒（MX1 VLPs）已与9NHAc-GD2（NHAcGD2）偶联，以获得MX1-NHAcGD2偶联物。有趣的是，用这种偶联物进行疫苗接种在小鼠体内产生了强烈的抗NHAcGD2 IgG反应，平均IgG滴度超过300万。更有趣的是，由MX1-NHAcGD2偶联物诱导的抗体与IMR-32神经母细胞瘤细胞结合良好，并对IMR-32细胞具有强大的补体依赖性细胞毒性（CDC）作用。受9NHAc-GD2抗原优势的启发，我们还设计了另一种9NHAc修饰的神经节苷脂抗原9NHAc-GD3（NHAcGD3），以克服9-乙酰化-GD3的水解不稳定性。通过将NHAcGD3与MX1 VLP偶联，构建了MX1-NHAcGD3偶联物。令人惊讶的是，接种MX1-NHAcGD3可引发高抗NHAcGD3 IgG抗体，这些抗体能有效识别人类恶性黑色素瘤SK-MEL-28细胞，并对该细胞系具有显著的CDC作用。本研究提供了具有广阔临床转化前景的新型MX1-NHAcGD2和MX1-NHAcGD3偶联物，有望成为抗癌疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/093a/10875654/c1136ceffa98/d3ra08923a-f7.jpg
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