Extracellular Vesicles Hybrid Plasmid-loaded Lipid Nanovesicles for Synergistic Cancer Immunotherapy

Overview

Journal Mater Today Bio

Specialty Biomedical Engineering

Date 2023 Nov 9

PMID 37942423

Authors

Qing Tong

Kexin Li

Fanwei Huang

Yun Dai

Tao Zhang

Munawaer Muaibati

Abasi Abuduyilimu

Xiaoyuan Huang

Affiliations

Soon will be listed here.

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 (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.

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References

Saxena M, van der Burg S, Melief C, Bhardwaj N . Therapeutic cancer vaccines. Nat Rev Cancer. 2021; 21(6):360-378. DOI: 10.1038/s41568-021-00346-0. View

Bittel M, Reichert P, Sarfati I, Dressel A, Leikam S, Uderhardt S . Visualizing transfer of microbial biomolecules by outer membrane vesicles in microbe-host-communication in vivo. J Extracell Vesicles. 2021; 10(12):e12159. PMC: 8524437. DOI: 10.1002/jev2.12159. View

Park K, Svennerholm K, Crescitelli R, Lasser C, Gribonika I, Lotvall J . Synthetic bacterial vesicles combined with tumour extracellular vesicles as cancer immunotherapy. J Extracell Vesicles. 2021; 10(9):e12120. PMC: 8254025. DOI: 10.1002/jev2.12120. View

Larson R, Kann M, Bailey S, Haradhvala N, Montero Llopis P, Bouffard A . CAR T cell killing requires the IFNγR pathway in solid but not liquid tumours. Nature. 2022; 604(7906):563-570. DOI: 10.1038/s41586-022-04585-5. View

Yu Y, Cheng Q, Ji X, Chen H, Zeng W, Zeng X . Engineered drug-loaded cellular membrane nanovesicles for efficient treatment of postsurgical cancer recurrence and metastasis. Sci Adv. 2022; 8(49):eadd3599. PMC: 9733928. DOI: 10.1126/sciadv.add3599. View

Toyofuku M, Nomura N, Eberl L . Types and origins of bacterial membrane vesicles. Nat Rev Microbiol. 2018; 17(1):13-24. DOI: 10.1038/s41579-018-0112-2. View

Postow M, Sidlow R, Hellmann M . Immune-Related Adverse Events Associated with Immune Checkpoint Blockade. N Engl J Med. 2018; 378(2):158-168. DOI: 10.1056/NEJMra1703481. View

Yoon H, Cho C, Yun M, Jang S, You H, Kim J . Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice. Nat Microbiol. 2021; 6(5):563-573. DOI: 10.1038/s41564-021-00880-5. View

Ye T, Li F, Ma G, Wei W . Enhancing therapeutic performance of personalized cancer vaccine via delivery vectors. Adv Drug Deliv Rev. 2021; 177:113927. DOI: 10.1016/j.addr.2021.113927. View

10.

Miao L, Zhang Y, Huang L . mRNA vaccine for cancer immunotherapy. Mol Cancer. 2021; 20(1):41. PMC: 7905014. DOI: 10.1186/s12943-021-01335-5. View

11.

Song W, Shen L, Wang Y, Liu Q, Goodwin T, Li J . Synergistic and low adverse effect cancer immunotherapy by immunogenic chemotherapy and locally expressed PD-L1 trap. Nat Commun. 2018; 9(1):2237. PMC: 5993831. DOI: 10.1038/s41467-018-04605-x. View

12.

Zhang L, Zhao J, Hu X, Wang C, Jia Y, Zhu C . A Peritumorally Injected Immunomodulating Adjuvant Elicits Robust and Safe Metalloimmunotherapy against Solid Tumors. Adv Mater. 2022; 34(41):e2206915. DOI: 10.1002/adma.202206915. View

13.

Plovier H, Everard A, Druart C, Depommier C, Van Hul M, Geurts L . A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med. 2016; 23(1):107-113. DOI: 10.1038/nm.4236. View

14.

Derosa L, Routy B, Thomas A, Iebba V, Zalcman G, Friard S . Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer. Nat Med. 2022; 28(2):315-324. PMC: 9330544. DOI: 10.1038/s41591-021-01655-5. View

15.

Zhong S, Li Q, Wen C, Li Y, Zhou Y, Jin Z . Interferon α facilitates anti-HBV cellular immune response in a B cell-dependent manner. Antiviral Res. 2022; 207:105420. DOI: 10.1016/j.antiviral.2022.105420. View

16.

Hammerich L, Marron T, Upadhyay R, Svensson-Arvelund J, Dhainaut M, Hussein S . Systemic clinical tumor regressions and potentiation of PD1 blockade with in situ vaccination. Nat Med. 2019; 25(5):814-824. DOI: 10.1038/s41591-019-0410-x. View

17.

Yarchoan M, Johnson 3rd B, Lutz E, Laheru D, Jaffee E . Targeting neoantigens to augment antitumour immunity. Nat Rev Cancer. 2017; 17(4):209-222. PMC: 5575801. DOI: 10.1038/nrc.2016.154. View

18.

Depommier C, Everard A, Druart C, Plovier H, Van Hul M, Vieira-Silva S . Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med. 2019; 25(7):1096-1103. PMC: 6699990. DOI: 10.1038/s41591-019-0495-2. View

19.

Li Q, Shi Z, Zhang F, Zeng W, Zhu D, Mei L . Symphony of nanomaterials and immunotherapy based on the cancer-immunity cycle. Acta Pharm Sin B. 2022; 12(1):107-134. PMC: 8799879. DOI: 10.1016/j.apsb.2021.05.031. View

20.

Johnson D, Nebhan C, Moslehi J, Balko J . Immune-checkpoint inhibitors: long-term implications of toxicity. Nat Rev Clin Oncol. 2022; 19(4):254-267. PMC: 8790946. DOI: 10.1038/s41571-022-00600-w. View