Cited by 187Immunotherapy and Immune ResponsesRNA Interference and Gene DeliveryNanoparticle-Based Drug Delivery

Lipopolyplex potentiates anti-tumor immunity of mRNA-based vaccination

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Persano, Stefano, Guevara, Maria L., Li, Zhaoqi, Mai, Junhua, Ferrari, Mauro, Pompa, Pier Paolo, Shen, Haifa·2017·Biomaterials

Abstract

mRNA-based vaccines have the benefit of triggering robust anti-cancer immunity without the potential danger of genome integration from DNA vaccines or the limitation of antigen selection from peptide vaccines. Yet, a conventional mRNA vaccine comprising of condensed mRNA molecules in a positively charged protein core structure is not effectively internalized by the antigen-presenting cells. It cannot offer sufficient protection for mRNA molecules from degradation by plasma and tissue enzymes either. Here, we have developed a lipopolyplex mRNA vaccine that consists of a poly-(β-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000 (EDOPC/DOPE/DSPE-PEG) lipid shell. This core-shell structured mRNA vaccine enters dendritic cells through macropinocytosis. It displayed intrinsic adjuvant activity by potently stimulating interferon-β and interleukin-12 expression in dendritic cells through Toll-like receptor 7/8 signaling. Dendritic cells treated with the mRNA vaccine displayed enhanced antigen presentation capability. Mice bearing lung metastatic B16-OVA tumors expressing the ovalbumin antigen were treated with the lipopolyplex mRNA, and over 90% reduction of tumor nodules was observed. Collectively, this core-shell structure offers a promising platform for mRNA vaccine development.

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Crossref · 10.1016/j.biomaterials.2017.02.019

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  • The findings of this study revealed that, compared with naked PbAE-mRNA, cellular transfection efficiency was greatly improved when LPP-coated PbAE-mRNA was used.

    “The findings of this study revealed that, compared with naked PbAE-mRNA, cellular transfection efficiency was greatly improved when LPP-coated PbAE-mRNA was used.”

    From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [326]

  • Moreover, this LPP-based mRNA vaccine exhibited intrinsic adjuvant activity, which stimulates dendritic cells (DCs) to secrete cytokines and inhibit tumor growth by activating the TLR7/8 signaling pathway, resulting in a significant antitumor activity.

    “Moreover, this LPP-based mRNA vaccine exhibited intrinsic adjuvant activity, which stimulates dendritic cells (DCs) to secrete cytokines and inhibit tumor growth by activating the TLR7/8 signaling pathway, resulting in a significant antitumor activity.”

    From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [326]

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  1. [39]Fotin-Mleczek M Duchardt KM Lorenz C Pfeiffer R Ojkic-Zrna S Probst J Messenger RNA-based vaccines with dual activity induce balanced TLR-7 dependent adaptive immune responses and provide antitumor activity Journal of immunotherapy (Hagerstown, Md: 1997) 2011 34 1 1 15 21150709

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Authors
Persano, S., Guevara, M. L., Li, Z., Mai, J., Ferrari, M., Pompa, P. P., & Shen, H.
Affiliations
  • Houston Methodist (US)
  • Italian Institute of Technology (IT)
Corresponding author
Shen, Haifa
Venue
Biomaterials
Publisher
Elsevier BV
Published
2017-05
Volume
125
Pages
81-89
ISSN
0142-9612 (ISSN-L)
OpenAlex
W2589539207
Cited by
187
References
43
Citations by year
2026: 10 · 2025: 26 · 2024: 30 · 2023: 28 · 2022: 26 · 2021: 18 · 2020: 20 · 2019: 13 · 2018: 12 · 2017: 4
FWCI
6.06
Type
journal article
Language
en
Open access
Locations
  • Biomaterials (acceptedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (1R01CA193880-01A1, U54CA210181)
  • U.S. Department of Defense (W81XWH-12-1-0414)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
mRNA vaccines, lipopolyplexes, poly(β-amino ester), core-shell nanoparticles, dendritic cells, macropinocytosis, interferon-beta, IL-12, antigen presentation, lung metastasis, B16-OVA tumor, antitumor immunity, vaccine adjuvants, lipid shell
MeSH terms
Animals, Drug Synergism, Female, Liposomes, Male, Mice, Inbred C57BL, Neoplasms, Experimental, RNA, Messenger, Transfection, Treatment Outcome, Cancer Vaccines, Cell Line, Tumor, Mice

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