Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo.
Open accessAbstract
Immunization with defined tumor antigens is currently limited to a small number of cancers where candidates for tumor rejection antigens have been identified. In this study we investigated whether pulsing dendritic cells (DC) with tumor-derived RNA is an effective way to induce CTL and tumor immunity. DC pulsed with in vitro synthesized chicken ovalbumin (OVA) RNA were more effective than OVA peptide-pulsed DC in stimulating primary, OVA-specific CTL responses in vitro. DC pulsed with unfractionated RNA (total or polyA+) from OVA-expressing tumor cells were as effective as DC pulsed with OVA peptide at stimulating CTL responses. Induction of OVA-specific CTL was abrogated when polyA+ RNA from OVA-expressing cells was treated with an OVA-specific antisense oligodeoxynucleotide and RNase H, showing that sensitization of DC was indeed mediated by OVA RNA. Mice vaccinated with DC pulsed with RNA from OVA-expressing tumor cells were protected against a challenge with OVA-expressing tumor cells. In the poorly immunogenic, highly metastatic, B16/F10.9 tumor model a dramatic reduction in lung metastases was observed in mice vaccinated with DC pulsed with tumor-derived RNA (total or polyA+, but not polyA- RNA). The finding that RNA transcribed in vitro from cDNA cloned in a bacterial plasmid was highly effective in sensitizing DC shows that amplification of the antigenic content from a small number of tumor cells is feasible, thus expanding the potential use of RNA-pulsed DC-based vaccines for patients bearing very small, possibly microscopic, tumors.
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Production of MHC-associated epitopes and priming of cytotoxic T-lymphocytes is achieved even if the full-length protein encoded by the transferred RNA cannot be detected in DCs.
“However, it has also been reported that the production of MHC-associated epitopes and priming of cytotoxic T-lymphocytes is achieved even if the full-length protein encoded by the transferred RNA cannot be detected in DCs.42,48”
From Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells (2006) · cites this paper as [42]
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- Authors
- Boczkowski, D., Nair, S. K., Snyder, D., & Gilboa, E.
- Affiliations
- Duke Medical Center (US)
- Venue
- The Journal of experimental medicine
- Publisher
- Rockefeller University Press
- Published
- 1996-08-01
- Volume
- 184
- Issue
- 2
- Pages
- 465-472
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2192710
- OpenAlex
- W2167614869
- Cited by
- 915
- References
- 1
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 24 · 2023: 34 · 2022: 32 · 2021: 27 · 2020: 18 · 2019: 10 · 2018: 18 · 2017: 8 · 2016: 15 · 2015: 18 · 2014: 16 · 2013: 27 · 2012: 20
- FWCI
- 14.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- dendritic cells, antigen presentation, cytotoxic T lymphocytes, cancer vaccination, chicken ovalbumin, polyadenylated RNA, antisense oligodeoxynucleotides, cancer vaccines, lung metastasis, tumor rejection antigens
- MeSH terms
- Animals, Antigen-Presenting Cells, Base Sequence, Cytotoxicity, Immunologic, Dendritic Cells, Immunity, Cellular, Mice, Inbred C57BL, Molecular Sequence Data, Ovalbumin, RNA, RNA, Messenger, T-Lymphocytes, Cytotoxic, Mice
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