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Development of a Cancer Vaccine Using In Vivo Click‐Chemistry‐Mediated Active Lymph Node Accumulation for Improved Immunotherapy
Author(s) -
Qin Hao,
Zhao Ruifang,
Qin Yuting,
Zhu Jin,
Chen Long,
Di Chunzhi,
Han Xuexiang,
Cheng Keman,
Zhang Yinlong,
Zhao Ying,
Shi Jian,
Anderson Gregory J.,
Zhao Yuliang,
Nie Guangjun
Publication year - 2021
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.202006007
Subject(s) - in vivo , adjuvant , lymph node , cancer vaccine , click chemistry , cancer immunotherapy , cancer research , immune system , lymphatic system , immunotherapy , cd8 , t cell , antigen , immunology , materials science , chemistry , biology , combinatorial chemistry , microbiology and biotechnology
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 257–264 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.