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

✍ Scribed by Edward I. Cho; Chunrui Tan; Gary K. Koski; Peter A. Cohen; Suyu Shu; Walter T. Lee

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 214 KB
• Volume: 32
• Category: Article
• ISSN: 1043-3074
• DOI: 10.1002/hed.21241

✦ Synopsis

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. © 2009 Wiley Periodicals, Inc. Head Neck, 2010