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 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.
Cho
Edward I
EI
Head and Neck Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Tan
Chunrui
C
Koski
Gary K
GK
Cohen
Peter A
PA
Shu
Suyu
S
Lee
Walter T
WT
D000276:Adjuvants, Immunologic; D000818:Animals; D002459:Cell Fusion / Q000379:methods*; D003713:Dendritic Cells / Q000276:immunology*; D004558:Electric Stimulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006822:Hybrid Cells / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D018664:Interleukin-12 / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D008546:Melanoma, Experimental / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D051193:Toll-Like Receptors / Q000819:agonists*; D014614:Vaccines, Synthetic
D000276:Adjuvants, Immunologic; D011993:Recombinant Fusion Proteins; D051193:Toll-Like Receptors; D014614:Vaccines, Synthetic; D018664:Interleukin-12