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具有内置佐剂的多功能蛋白质偶联物（佐剂-蛋白质-抗原）作为癌症疫苗可增强强效免疫反应。

Multifunctional Protein Conjugates with Built-in Adjuvant (Adjuvant-Protein-Antigen) as Cancer Vaccines Boost Potent Immune Responses.

作者信息

Du Jing-Jing, Wang Chang-Wei, Xu Wen-Bo, Zhang Lian, Tang Yuan-Kai, Zhou Shi-Hao, Gao Xiao-Fei, Yang Guang-Fu, Guo Jun

机构信息

Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, Hubei International Scientific and Technological Cooperation Base of Pesticide and Green Synthesis, International Joint Research Center for Intelligent Bio-sensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan, Hubei 430079, China.

Jiangxi Key Laboratory for Mass Spectrometry and Instrumentation, East China University of Technology, Nanchang, Jiangxi 330013, China.

出版信息

iScience. 2020 Mar 27;23(3):100935. doi: 10.1016/j.isci.2020.100935. Epub 2020 Feb 24.

DOI:10.1016/j.isci.2020.100935
PMID:32146328
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7063246/
Abstract

Many cancer vaccines are not successful in clinical trials, mainly due to the challenges associated with breaking immune tolerance. Herein, we report a new strategy using an adjuvant-protein-antigen (three-in-one protein conjugates with built-in adjuvant) as an anticancer vaccine, in which both the adjuvant (small-molecule TLR7 agonist) and tumor-associated antigen (mucin 1, MUC1) are covalently conjugated to the same carrier protein (BSA). It is shown that the protein conjugates with built-in adjuvant can increase adjuvant's stimulation, prevent adjuvant's systemic toxicities, facilitate the codelivery of adjuvants and antigens, and enhance humoral and cellular immune responses. The IgG antibody titers elicited by the self-adjuvanting three-in-one protein conjugates were significantly higher than those elicited by the vaccine mixed with TLR7 agonist (more than 15-fold) or other traditional adjuvants. Importantly, the potent immune responses against cancer cells suggest that this new vaccine construct is an effective strategy for the personalized antitumor immunotherapy.

摘要

许多癌症疫苗在临床试验中未取得成功，主要是由于打破免疫耐受存在挑战。在此，我们报告一种新策略，即使用佐剂 - 蛋白质 - 抗原（内置佐剂的三合一蛋白质偶联物）作为抗癌疫苗，其中佐剂（小分子TLR7激动剂）和肿瘤相关抗原（粘蛋白1，MUC1）均共价偶联至同一载体蛋白（牛血清白蛋白，BSA）。结果表明，内置佐剂的蛋白质偶联物可增强佐剂的刺激作用，防止佐剂的全身毒性，促进佐剂和抗原的共递送，并增强体液免疫和细胞免疫反应。自佐剂化的三合一蛋白质偶联物引发的IgG抗体滴度显著高于与TLR7激动剂混合的疫苗（超过15倍）或其他传统佐剂引发的滴度。重要的是，针对癌细胞的强效免疫反应表明，这种新型疫苗构建体是个性化抗肿瘤免疫疗法的有效策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a9/7063246/7787539a452b/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a9/7063246/dfeee8892960/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a9/7063246/a404f74fbb96/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a9/7063246/35a4b612ee1b/sc2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a9/7063246/f8c983986603/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a9/7063246/76343d48aeff/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a9/7063246/e8945f8bcf93/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a9/7063246/d73e5e15cf65/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a9/7063246/cae681ceefe3/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a9/7063246/881172ceefb8/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a9/7063246/7787539a452b/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a9/7063246/dfeee8892960/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a9/7063246/a404f74fbb96/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a9/7063246/35a4b612ee1b/sc2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a9/7063246/f8c983986603/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a9/7063246/76343d48aeff/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a9/7063246/e8945f8bcf93/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a9/7063246/d73e5e15cf65/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a9/7063246/cae681ceefe3/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a9/7063246/881172ceefb8/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a9/7063246/7787539a452b/gr7.jpg

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