Multifunctional Protein Conjugates with Built-in Adjuvant (Adjuvant-Protein-Antigen) as Cancer Vaccines Boost Potent Immune Responses
Multifunctional Protein Conjugates with Built-in Adjuvant (Adjuvant-Protein-Antigen) as Cancer Vaccines Boost Potent Immune Responses
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多功能蛋白质缀合物与内置佐剂（佐剂-蛋白质-抗原）作为癌症疫苗可增强有效的免疫反应
DOI：
10.1016/j.isci.2020.100935
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发表时间：
2020-03-27
期刊：
影响因子：
5.8
通讯作者：
Guo, Jun
中科院分区：
文献类型：
--
作者：
Du, Jing-Jing;Wang, Chang-Wei;Guo, Jun
许多癌症疫苗在临床试验中未获成功，主要是由于打破免疫耐受方面存在挑战。在此，我们报道一种新策略，即使用一种佐剂 - 蛋白质 - 抗原（具有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）都共价偶联到同一载体蛋白（牛血清白蛋白，BSA）上。研究表明，具有内置佐剂的蛋白质偶联物能够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同递送，并增强体液免疫和细胞免疫反应。由这种具有自佐剂作用的三合一蛋白质偶联物引发的IgG抗体滴度显著高于由与TLR7激动剂混合的疫苗（超过15倍）或其他传统佐剂所引发的抗体滴度。重要的是，针对癌细胞的强大免疫反应表明，这种新的疫苗构建体是个性化抗肿瘤免疫治疗的一种有效策略。
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.