Pancreatic cancer has a dismal prognosis, and treatment options for patients with locally advanced or metastatic disease are limited. Early
tumor progression after standard chemo- and or
radiotherapy remains a major concern in managing these patients. Treating
pancreatic cancer patients with the
Toll-like receptor 3 (TLR-3) agonist
rintatolimod (Ampligen®) was effective in boosting the immune response.
Rintatolimod acts via the TLR-3 receptor on several immune cells. However, the TLR-3 expression pattern in
pancreatic cancer cells and how
rintatolimod affects
pancreatic cancer cells have not yet been investigated. The TLR-3
protein and
mRNA expression were evaluated in thirteen PDAC tissue samples as well as in the human PDAC (hPDAC) cell lines CFPAC-1, MIAPaCa-2, and PANC-1 using immunohistochemistry and multiplexed gene expression analysis, respectively. The direct anti-
tumor effects of
rintatolimod were investigated using a proliferation and migration assay after different incubation time points with increasing concentrations of
rintatolimod (ranging from 0.05 to 0.4 mg/ml). The TLR-3
protein and
mRNA expression were heterogeneous between the PDAC tissue samples and the three hPDAC cell lines. TLR-3
protein and
mRNA expression were high in CFPAC-1, moderate in MIAPaCa-2, and undetectable in PANC-1.
Rintatolimod three-day treatment resulted in significantly reduced proliferation of CFPAC-1 cells compared to vehicle-treated control cells. In addition, after 24 hours,
rintatolimod-treated CFPAC-1 cells showed less cell migration compared to vehicle-treated control cells, although this difference was not statistically significant. Lastly, we identified fifteen genes, altered with a Log2 FOC > |1.0| in
rintatolimod-treated CFPAC-1 cells, which were significantly related to three
transcription factors (NFKB1, RELA, and SP1) regulating the TLR-3 signaling pathway. In conclusion, we propose that
rintatolimod treatment might have a direct TLR-3-dependent anti-tumoral effect on
pancreatic cancer cells expressing TLR-3.