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金纳米颗粒呈递的α-半乳糖神经酰胺佐剂增强基于 MUC1 抗原的肿瘤疫苗的抗肿瘤免疫应答。

The Adjuvant of α-Galactosylceramide Presented by Gold Nanoparticles Enhances Antitumor Immune Responses of MUC1 Antigen-Based Tumor Vaccines.

机构信息

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and KLMDASR of Tianjin, Nankai University, Tianjin 300353, People's Republic of China.

College of Life Sciences, Nankai University, Tianjin 300071, People's Republic of China.

出版信息

Int J Nanomedicine. 2021 Jan 14;16:403-420. doi: 10.2147/IJN.S273883. eCollection 2021.

DOI:10.2147/IJN.S273883
PMID:33469292
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7813472/
Abstract

BACKGROUND

Therapeutic tumor vaccines are one of the most promising strategies and have attracted great attention in cancer treatment. However, most of them have shown unsatisfactory immunogenicity, there are still few available vaccines for clinical use. Therefore, there is an urgent demand to develop novel strategies to improve the immune efficacy of antitumor vaccines.

PURPOSE

This study aimed to develop novel adjuvants and carriers to enhance the immune effect of MUC1 glycopeptide antigen-based antitumor vaccines.

METHODS

An antitumor vaccine was developed, in which MUC1 glycopeptide was used as tumor-associated antigen, α-GalCer served as an immune adjuvant and AuNPs was a multivalent carrier.

RESULTS

Immunological evaluation results indicated that the constructed vaccines enabled a significant antibody response. FACS analysis and immunofluorescence assay showed that the induced antisera exhibited a specific binding with MUC1 positive MCF-7 cells. Moreover, the induced antibody can mediate CDC to kill MCF-7 cells. Besides stimulating B cells to produce MUC1-specific antibodies, the prepared vaccines also induced MUC1-specific CTLs in vitro. Furthermore, the vaccines significantly delayed tumor development in tumor-bearing mice model.

CONCLUSION

These results showed that the construction of vaccines by presenting α-GalCer adjuvant and an antigen on gold nanoparticles offers a potential strategy to improve the antitumor response in cancer immunotherapy.

摘要

背景

治疗性肿瘤疫苗是最有前途的策略之一，在癌症治疗中引起了极大的关注。然而，它们中的大多数表现出令人不满意的免疫原性，临床上可用的疫苗仍然很少。因此，迫切需要开发新的策略来提高抗肿瘤疫苗的免疫效果。

目的

本研究旨在开发新型佐剂和载体，以增强基于 MUC1 糖肽抗原的抗肿瘤疫苗的免疫效果。

方法

研制了一种抗肿瘤疫苗，其中 MUC1 糖肽作为肿瘤相关抗原，α-GalCer 作为免疫佐剂，AuNPs 作为多价载体。

结果

免疫学评价结果表明，构建的疫苗能够引起显著的抗体反应。FACS 分析和免疫荧光试验表明，诱导的抗血清与 MUC1 阳性 MCF-7 细胞具有特异性结合。此外，诱导的抗体可以介导 CDC 杀伤 MCF-7 细胞。该疫苗不仅能刺激 B 细胞产生 MUC1 特异性抗体，还能在体外诱导 MUC1 特异性 CTL。此外，疫苗还显著延缓了荷瘤小鼠模型中的肿瘤发展。

结论

这些结果表明，在金纳米粒子上呈现α-GalCer 佐剂和抗原构建疫苗为提高癌症免疫治疗中的抗肿瘤反应提供了一种潜在策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f3f/7813472/1365b60f1fc1/IJN-16-403-g0013.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f3f/7813472/1365b60f1fc1/IJN-16-403-g0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f3f/7813472/501064b26cfc/IJN-16-403-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f3f/7813472/086e5128f627/IJN-16-403-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f3f/7813472/c1dde6ed19c8/IJN-16-403-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f3f/7813472/6d6526d595a4/IJN-16-403-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f3f/7813472/5aba40efbddc/IJN-16-403-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f3f/7813472/6fe557586ae2/IJN-16-403-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f3f/7813472/48155684b686/IJN-16-403-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f3f/7813472/2e0efbebac64/IJN-16-403-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f3f/7813472/3d5debce6f00/IJN-16-403-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f3f/7813472/4d345c315825/IJN-16-403-g0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f3f/7813472/debf01b91258/IJN-16-403-g0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f3f/7813472/6b8ea9e9bc7b/IJN-16-403-g0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f3f/7813472/1365b60f1fc1/IJN-16-403-g0013.jpg

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