Development of a Cancer Vaccine Using In Vivo Click-Chemistry-Mediated Active Lymph Node Accumulation for Improved Immunotherapy

Hao Qin, Ruifang Zhao, Yuting Qin, Jin Zhu, Long Chen, Chunzhi Di, Xuexiang Han, Keman Cheng, Yinlong Zhang, Ying Zhao, Jian Shi, Gregory J. Anderson, Yuliang Zhao, Guangjun Nie

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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 OVA257–264 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.

Original languageEnglish (US)
Article number2006007
JournalAdvanced Materials
Volume33
Issue number20
DOIs
StatePublished - May 20 2021

Keywords

  • cancer vaccines
  • click chemistry
  • immunotherapy
  • lymph node targeting

ASJC Scopus subject areas

  • Materials Science(all)
  • Mechanics of Materials
  • Mechanical Engineering

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