Systemic activation of antigen-presenting cells via RNA-loaded nanoparticles
Open accessAbstract
While RNA-pulsed dendritic cell (DC) vaccines have shown promise, the advancement of cellular therapeutics is fraught with developmental challenges. To circumvent the challenges of cellular immunotherapeutics, we developed clinically translatable nanoliposomes that can be combined with tumor-derived RNA to generate personalized tumor RNA-nanoparticles (NPs) with considerable scale-up capacity. RNA-NPs bypass MHC restriction, are amenable to central distribution, and can provide near immediate immune induction. We screened commercially available nanoliposomal preparations and identified the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as an efficient mRNA courier to antigen-presenting cells (APCs). When administered intravenously, RNA-NPs mediate systemic activation of APCs in reticuloendothelial organs such as the spleen, liver, and bone marrow. RNA-NPs increase percent expression of MHC class I/II, B7 co-stimulatory molecules, and maturation markers on APCs (all vital for T-cell activation). RNA-NPs also increase activation markers on tumor APCs and elicit potent expansion of antigen-specific T-cells superior to peptide vaccines formulated in complete Freund's adjuvant. We demonstrate that both model antigen-encoding and physiologically-relevant tumor-derived RNA-NPs expand potent antitumor T-cell immunity. RNA-NPs were shown to induce antitumor efficacy in a vaccine model and functioned as a suitable alternative to DCs in a stringent cellular immunotherapy model for a radiation/temozolomide resistant invasive murine high-grade glioma. Although cancer vaccines have suffered from weak immunogenicity, we have advanced a RNA-NP formulation that systemically activates host APCs precipitating activated T-cell frequencies necessary to engender antitumor efficacy. RNA-NPs can thus be harnessed as a more feasible and effective immunotherapy to re-program host-immunity.
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i.v. administration of mRNA vaccines has been shown to induce stronger antigen-specific cytotoxic T cell responses compared with local injection.
“For example, i.v. administration of mRNA vaccines has been shown to induce stronger antigen-specific cytotoxic T cell responses compared with local injection26,148,149.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [148]
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- Authors
- Sayour, E. J., De Leon, G., Pham, C., Grippin, A., Kemeny, H., Chua, J., Huang, J., Sampson, J. H., Sanchez-Perez, L., Flores, C., & Mitchell, D. A.
- Affiliations
- University of Florida (US)
- Center for Brain Tumor Therapy, UF Brain Tumor Immunotherapy Program, McKnight Brain Institute, Department of Neurosurgery, University of Florida, Gainesville, FL, USA
- Duke Medical Center (US)
- Corresponding author
- Sayour, Elias J.
- ORCID
- Venue
- OncoImmunology
- Publisher
- Informa UK Limited
- Published
- 2016-11-18
- Volume
- 6
- Issue
- 1
- Pages
- e1256527
- ISSN
- 2162-4011 (ISSN-L)
- 2162-402X
- PMC
- PMC5283636
- OpenAlex
- W2551605225
- Cited by
- 93
- References
- 34
- Citations by year
- 2026: 3 · 2025: 13 · 2024: 15 · 2023: 14 · 2022: 12 · 2021: 13 · 2020: 8 · 2019: 9 · 2018: 6
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- OncoImmunology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- University of Florida
- National Institutes of Health
- National Cancer Institute (K08CA199224)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD040372)
- 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
- nanoliposomes, dendritic cell vaccine, antigen-presenting cells, DOTAP, B7 costimulatory molecules, T cell-mediated antitumor immunity, glioma, temozolomide resistance, radioresistance, personalized cancer vaccines
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