State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Functional Polymer Materials of Ministry of Education, College of Chemistry, Nankai University, Tianjin 300071, China.
The First Mobile Armed Police Crops, Tianjin 300192, P. R. China.
Nano Lett. 2020 Jun 10;20(6):4454-4463. doi: 10.1021/acs.nanolett.0c01230. Epub 2020 May 19.
Inspired by heat shock proteins (HSPs), a self-assembly nanochaperone (nChap) is developed as a novel nanovaccine for boosting antitumor immune responses. Taking advantage of HSP-like microdomains and surface-decorated mannose, this nChap can efficiently capture antigens and ferry them into the dendritic cells (DCs). Subsequently, the nChap can blast lysosomes by transforming the structure and property of surface microdomains, thereby promoting antigen escape and enhancing their cross-presentation in cytoplasm. As a result, the nChap-based nanovaccine can elicit both CD4+ and CD8+ T cell-based immune responses and shows an excellent preventive effect on melanoma. Further combination of the nanovaccine with antiprogrammed death-1 (anti-PD-1) checkpoint blockade offers effective inhibition on the growth of already-established melanoma. Therefore, this nC ap-based nanovaccine provides a simple and robust strategy in mimicking HSPs to realize structure-assisted antigen capture, surface-receptor-mediated DC internalization, and both activation of humoral immunity and cellular immunity, promising for efficient cancer immunotherapy.
受热休克蛋白 (HSPs) 的启发，开发了一种自组装纳米伴侣 (nChap)，作为一种新型纳米疫苗，以增强抗肿瘤免疫反应。利用 HSP 样微区和表面修饰的甘露糖，这种 nChap 可以有效地捕获抗原，并将其运送到树突状细胞 (DCs) 中。随后，nChap 可以通过改变表面微区的结构和性质来爆破溶酶体，从而促进抗原逃逸，并增强其在细胞质中的交叉呈递。因此，基于 nChap 的纳米疫苗可以引发基于 CD4+和 CD8+T 细胞的免疫反应，并对黑色素瘤表现出优异的预防效果。进一步将纳米疫苗与抗程序性死亡-1 (抗 PD-1) 检查点阻断联合使用，可有效抑制已建立的黑色素瘤的生长。因此，这种基于 nCap 的纳米疫苗为模拟 HSPs 以实现结构辅助抗原捕获、表面受体介导的 DC 内化以及体液免疫和细胞免疫的双重激活提供了一种简单而强大的策略，有望实现高效的癌症免疫治疗。
