Extracellular vesicles hybrid plasmid-loaded lipid nanovesicles for synergistic cancer immunotherapy

Qing Tong; Kexin Li; Fanwei Huang; Yun Dai; Tao Zhang; Munawaer Muaibati; Abasi Abuduyilimu; Xiaoyuan Huang

doi:10.1016/j.mtbio.2023.100845

Extracellular vesicles hybrid plasmid-loaded lipid nanovesicles for synergistic cancer immunotherapy

Mater Today Bio. 2023 Oct 27:23:100845. doi: 10.1016/j.mtbio.2023.100845. eCollection 2023 Dec.

Authors

Qing Tong^{1

2}, Kexin Li^{1

2}, Fanwei Huang^{1

2}, Yun Dai^{1

2}, Tao Zhang^{1

2}, Munawaer Muaibati^{1

2}, Abasi Abuduyilimu^{1

2}, Xiaoyuan Huang^{1

2}

Affiliations

¹ National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Abstract

Combination immunotherapy of cancer vaccines with immune checkpoint inhibitors (ICIs) represents a promising therapeutic strategy for immunosuppressed and cold tumors. However, this strategy still faces challenges, including the limited therapeutic efficacy of cancer vaccines and immune-related adverse events associated with systematic delivery of ICIs. Herein, we demonstrate the antitumor immune response induced by outer membrane vesicle from Akkermansia muciniphila (Akk-OMV), which exhibites a favorable safety profile, highlighting the potential application as a natural and biocompatible self-adjuvanting vesicle. Utilizing tumor cell-derived exosome as an antigen source and Akk-OMV as a natural adjuvant, we construct a cancer vaccine formulation of extracellular vesicles hybrid lipid nanovesicles (Lipo@HEV) for enhanced prophylactic and therapeutic vaccination by promoting dendritic cell (DC) maturation in lymph node and activating cytotoxic T cell (CTL) response. The Lipo@HEV is further loaded with plasmid to enable gene therapy-mediated PD-L1 blockade upon peritumoral injection. Meanwhile, it penetrates into lymph node to initiate DC maturation and CTL activation, synergistically inhibiting the established tumor. The fabrication of extracellular vesicles hybrid plasmid-loaded lipid nanovesicles reveals a promising gene therapy-guided and vesicle-based hybrid system for therapeutic cancer vaccination and synergistic immunotherapy strategy.

Keywords: Akkermansia muciniphila; Cancer vaccine; Extracellular vesicles; Hybrid lipid nanovesicles; Immune checkpoint blockade; Liposomes.