CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, China, Beijing, 100190, China.
Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China.
Adv Mater. 2021 May;33(20):e2006007. doi: 10.1002/adma.202006007. Epub 2021 Mar 31.
Due to their ability to elicit a potent immune reaction with low systemic toxicity, cancer vaccines represent a promising strategy for treating tumors. Considerable effort has been directed toward improving the in vivo efficacy of cancer vaccines, with direct lymph node (LN) targeting being the most promising approach. Here, a click-chemistry-based active LN accumulation system (ALAS) is developed by surface modification of lymphatic endothelial cells with an azide group, which provide targets for dibenzocyclooctyne (DBCO)-modified liposomes, to improve the delivery of encapsulated antigen and adjuvant to LNs. When loading with OVA peptide and poly(I:C), the formulation elicits an enhanced CD8 T cell response in vivo, resulting in a much more efficient therapeutic effect and prolonged median survival of mice. Compared to treatment with DBCO-conjugated liposomes (DL)-Ag/Ad without the azide targeting, the percent survival of ALAS-vaccine-treated mice improves by 100% over 60 days. Altogether, the findings indicate that the novel ALAS approach is a powerful strategy to deliver vaccine components to LNs for enhanced antitumor immunity.
由于癌症疫苗具有引发强烈免疫反应和低全身毒性的能力，因此它们代表了治疗肿瘤的一种有前途的策略。人们已经投入了大量精力来提高癌症疫苗的体内疗效，直接针对淋巴结 (LN) 是最有前途的方法。在这里，通过在淋巴管内皮细胞表面修饰叠氮基团，开发了一种基于点击化学的主动 LN 积累系统 (ALAS)，为二苯并环辛炔 (DBCO)-修饰的脂质体提供了靶标，以改善包封抗原和佐剂向 LN 的递呈。当负载 OVA 肽和聚 (I:C) 时，该配方在体内引发增强的 CD8 T 细胞反应，从而产生更有效的治疗效果和延长小鼠的中位生存期。与没有叠氮靶向的 DBCO 缀合脂质体 (DL)-Ag/Ad 治疗相比，ALAS 疫苗治疗的小鼠的存活率在 60 天内提高了 100%。总的来说，这些发现表明，新型 ALAS 方法是一种将疫苗成分递送到 LN 以增强抗肿瘤免疫的有效策略。
