Toll-like receptor agonists as third signals for dendritic cell-tumor fusion vaccines

Edward I. Cho, Chunrui Tan, Gary K. Koski, Peter A Cohen, Suyu Shu, Walter T. Lee

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background. The aim of the present study was to evaluate the therapeutic efficacy of dendritic cell (DC)-tumor fusion hybrids with Toll-like receptor (TLR) agonists. Methods. DC-tumor fusion hybrids were generated by electrofusion and injected into the inguinal lymph nodes of C57BL/6 mice with 3-day established pulmonary metastases. Paired TLR agonists polyinosine:polycytadilic acid [poly(I:C)] and cytosine-phosphate-guanine (CpG) were then injected intraperitoneally. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate interleukin (IL)-12 production from the DC-tumor fusion hybrids in vitro. Results. Fusion + TLR agonists (60 metastases) had significantly fewer metastases than did the untreated control (262 metastases, p = .0001) and fusion alone (150 metastases, p = .02). ELISA showed that the DC-tumor fusion hybrids yielded 90 pg of IL-12 after TLR stimulation compared with 1610 pg from dendritic cells alone. Conclusions. CpG and poly(I:C) administered as a third signal with fusion hybrids as described significantly reduce melanoma metastasis compared with fusion hybrids alone. Fusion hybrids do not appear to be a significant source for IL-12 secretion.

Original languageEnglish (US)
Pages (from-to)700-707
Number of pages8
JournalHead and Neck
Volume32
Issue number6
DOIs
StatePublished - Jun 2010

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Keywords

  • Dendritic cells
  • Electrofusion
  • Third signal
  • Toll-like receptor agonists
  • Tumor immunology

ASJC Scopus subject areas

  • Otorhinolaryngology

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