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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Cho, EI; Tan, C; Koski, GK; Cohen, PA; Shu, S; Lee, WT

Published Date

  • June 2010

Published In

Volume / Issue

  • 32 / 6

Start / End Page

  • 700 - 707

PubMed ID

  • 19908319

Pubmed Central ID

  • 19908319

Electronic International Standard Serial Number (EISSN)

  • 1097-0347

International Standard Serial Number (ISSN)

  • 1043-3074

Digital Object Identifier (DOI)

  • 10.1002/hed.21241

Language

  • eng