Wei Lixia, Zhao Yu, Hu Xiaomeng, Tang Li
Institute of Materials Science and Engineering, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.
Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.
ACS Cent Sci. 2020 Mar 25;6(3):404-412. doi: 10.1021/acscentsci.9b01174. Epub 2020 Feb 3.
A versatile and highly effective platform remains a major challenge in the development of personalized cancer vaccines. Here, we devised a redox-responsive polycondensate neoepitope (PNE) through a reversible polycondensation reaction of peptide neoantigens and adjuvants together with a tracelessly responsive linker-monomer. Peptide-based neoantigens with diverse sequences and structures could be copolymerized with molecular adjuvants to form PNEs of high loading capacity for vaccine delivery without adding any carriers. The redox-responsive PNEs with controlled molecular weights and sizes efficiently targeted and accumulated in draining lymph nodes and greatly promoted the antigen capture and cross-presentation by professional antigen presenting cells. Mice immunized with PNEs showed markedly enhanced antigen-specific T cell response and the protective immunity against the tumor cell challenge.
在个性化癌症疫苗的研发中,一个多功能且高效的平台仍然是一项重大挑战。在此,我们通过肽新抗原与佐剂的可逆缩聚反应以及无痕响应连接体 - 单体,设计了一种氧化还原响应性缩聚物新表位(PNE)。具有不同序列和结构的基于肽的新抗原可与分子佐剂共聚,形成用于疫苗递送的高负载量PNE,而无需添加任何载体。具有可控分子量和尺寸的氧化还原响应性PNE有效地靶向并积聚在引流淋巴结中,并极大地促进了专业抗原呈递细胞的抗原捕获和交叉呈递。用PNE免疫的小鼠表现出显著增强的抗原特异性T细胞反应以及对肿瘤细胞攻击的保护性免疫。