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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1 August 1996
Article|
August 01 1996
Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo.
D Boczkowski,
D Boczkowski
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
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S K Nair,
S K Nair
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
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D Snyder,
D Snyder
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
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E Gilboa
E Gilboa
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
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D Boczkowski
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
S K Nair
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
D Snyder
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
E Gilboa
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1996) 184 (2): 465–472.
Citation
D Boczkowski, S K Nair, D Snyder, E Gilboa; Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo.. J Exp Med 1 August 1996; 184 (2): 465–472. doi: https://doi.org/10.1084/jem.184.2.465
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