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

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 e...

Full description

Saved in:
Bibliographic Details
Published in:Head & neck 2010-06, Vol.32 (6), p.700-707
Main Authors: Cho, Edward I., Tan, Chunrui, Koski, Gary K., Cohen, Peter A., Shu, Suyu, Lee, Walter T.
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic
Animals
Biological and medical sciences
Cell Fusion - methods
dendritic cells
Dendritic Cells - immunology
Electric Stimulation
electrofusion
Enzyme-Linked Immunosorbent Assay
Female
Hybrid Cells - immunology
Immunotherapy - methods
Interleukin-12 - metabolism
Lung Neoplasms - immunology
Lung Neoplasms - secondary
Lung Neoplasms - therapy
Medical sciences
Melanoma, Experimental - immunology
Melanoma, Experimental - secondary
Melanoma, Experimental - therapy
Mice
Mice, Inbred C57BL
Otorhinolaryngology. Stomatology
Recombinant Fusion Proteins - immunology
Specific Pathogen-Free Organisms
third signal
Toll-like receptor agonists
Toll-Like Receptors - agonists
tumor immunology
Vaccines, Synthetic
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
ISSN:1043-3074
1097-0347
DOI:10.1002/hed.21241