Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo

David Boczkowski, Smita K. Nair, David Snyder, Eli Gilboa

Research output: Contribution to journalArticle

726 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)465-472
Number of pages8
JournalJournal of Experimental Medicine
Volume184
Issue number2
StatePublished - Aug 1 1996
Externally publishedYes

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Ovalbumin
Antigen-Presenting Cells
Dendritic Cells
RNA
Neoplasms
Neoplasm Antigens
In Vitro Techniques
Peptides
Oligodeoxyribonucleotides
Chickens
Immunity
Immunization
Plasmids
Vaccines
Complementary DNA
Cell Count
Neoplasm Metastasis
Lung

ASJC Scopus subject areas

  • Immunology

Cite this

Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. / Boczkowski, David; Nair, Smita K.; Snyder, David; Gilboa, Eli.

In: Journal of Experimental Medicine, Vol. 184, No. 2, 01.08.1996, p. 465-472.

Research output: Contribution to journalArticle

Boczkowski, David ; Nair, Smita K. ; Snyder, David ; Gilboa, Eli. / Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. In: Journal of Experimental Medicine. 1996 ; Vol. 184, No. 2. pp. 465-472.
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