Toll-like receptor agonists as third signals for dendritic cell-tumor fusion vaccines.
Journal Article (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
Electronic International Standard Serial Number (EISSN)
- 1097-0347
Digital Object Identifier (DOI)
- 10.1002/hed.21241
Language
- eng
Conference Location
- United States