Personalized cancer vaccines from bacteria-derived outer membrane vesicles with antibody-mediated persistent uptake by dendritic cells

Jie Liang, Keman Cheng, Yao Li, Jiaqi Xu, Yiwei Chen, Nana Ma, Qingqing Feng, Fei Zhu, Xiaotu Ma, Tianjiao Zhang, Yale Yue, Guangna Liu, Xinjing Guo, Zhiqiang Chen, Xinwei Wang, Ruifang Zhao, Ying Zhao, Jian Shi, Xiao Zhao, Guangjun Nie

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Nanocarriers with intrinsic immune adjuvant properties can activate the innate immune system while delivering tumor antigen, thus efficiently facilitating antitumor adaptive immunity. Bacteria-derived outer membrane vesicles (OMVs) are an excellent candidate due to their abundance of pathogen associated molecular patterns. However, during the uptake of OMVs by dendritic cells (DCs), the interaction between lipopolysaccharide and toll-like receptor 4 induces rapid DC maturation and uptake blockage, a phenomenon we refer to as “maturation-induced uptake obstruction” (MUO). Herein we decorated OMV with the DC-targeting αDEC205 antibody (OMV-DEC), which endowed the nanovaccine with an uptake mechanism termed as “not restricted to maturation via antibody modifying” (Normandy), thereby overcoming the MUO phenomenon. We also proved the applicability of this nanovaccine in identifying the human tumor neoantigens through rapid antigen display. In summary, this engineered OMV represents a powerful nanocarrier for personalized cancer vaccines, and this antibody modification strategy provides a reference to remodel the DC uptake pattern in nanocarrier design.

Original languageEnglish (US)
Pages (from-to)23-36
Number of pages14
JournalFundamental Research
Volume2
Issue number1
DOIs
StatePublished - Jan 2022

Keywords

  • Antibody modification
  • Antigen display
  • Dendritic cell uptake
  • Myeloid derived suppressor cells
  • Outer membrane vesicles
  • Tumor vaccine

ASJC Scopus subject areas

  • General

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