Codelivery of mRNA with α-Galactosylceramide Using a New Lipopolyplex Formulation Induces a Strong Antitumor Response upon Intravenous Administration
Open accessAbstract
Recently, the use of mRNA-based vaccines for cancer immunotherapy has gained growing attention. Several studies have shown that mRNA delivered in a vectorized format can generate a robust and efficient immune response. In this work, a new lipopolyplex vector (multi-LP), incorporating the immune adjuvant α-galactosylceramide (α-GalCer) and a multivalent cationic lipid, was proposed for the in vivo delivery of mRNA into antigen-presenting cells. We demonstrate that dendritic cells (DCs) can be targeted in vivo by intravenous administration of a α-GalCer-/mRNA-loaded multi-LP vector, without the need for its functionalization with cell-specific antibodies or ligands. The multi-LP nanoparticles loaded with a reporter mRNA efficiently led to high expression of the enhanced green fluorescence protein in DCs both in vitro and in vivo, exhibiting an intrinsic selectivity for DCs. Finally, the TRP2-mRNA/α-GalCer-based multi-LP vaccine induced a significant therapeutic effect against a highly malignant B16-F10 melanoma tumor. This study provides the first evidence that a combination of antigen-mRNA and α-GalCer can be used as an effective antitumor vaccine, inducing strong innate and adaptive immune responses.
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LPPs have higher stability, low cytotoxicity, cell delivery and endosomal escape efficiency.
“LPPs have higher stability, low cytotoxicity, cell delivery and endosomal escape efficiency.327–329”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [328]
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- Authors
- Guevara, M. L., Jilesen, Z., Stojdl, D., & Persano, S.
- Affiliations
- University of Ottawa (CA)
- Corresponding author
- Stojdl, David
- Persano, Stefano
- ORCID
- Persano, Stefano
- Venue
- ACS Omega
- Publisher
- American Chemical Society (ACS)
- Published
- 2019-08-07
- Volume
- 4
- Issue
- 8
- Pages
- 13015-13026
- ISSN
- 2470-1343 (ISSN-L)
- PMC
- PMC6705043
- OpenAlex
- W2964505104
- Cited by
- 58
- References
- 61
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 5 · 2023: 8 · 2022: 11 · 2021: 13 · 2020: 6 · 2019: 1
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- ACS Omega (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Children's Hospital of Eastern Ontario Foundation
- National Cancer Institute of Canada
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- mRNA vaccines, alpha-galactosylceramide, lipopolyplexes, dendritic cell targeting, cationic lipid nanoparticles, cancer immunotherapy, B16F10 melanoma, antitumor immunity, innate and adaptive immunity, intravenous delivery
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