Tumor chemo-immunotherapy using gemcitabine and a synthetic dsRNA

Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon 97331, USA.
Cancer biology & therapy (Impact Factor: 3.63). 04/2008; 7(3):440-7. DOI: 10.4161/cbt.7.3.5423
Source: PubMed

ABSTRACT Both gemcitabine and synthetic double-stranded RNA (dsRNA) are known to be proapoptotic and immuno-stimulatory (-modulatory). We sought to evaluate the extent to which a combination therapy using gemcitabine and a synthetic dsRNA, polyinosine-cytosine (poly(I:C)), would improve the resultant anti-tumor activity. Using model lung and breast cancers in mice, we demonstrated that combination treatment of tumor-bearing mice with the poly(I:C) and gemcitabine synergistically delayed the tumor growth and prolonged the survival of the mice. The combination treatment also synergistically inhibited tumor cell growth in vitro and promoted more tumor cells to undergo apoptosis in vivo. Finally, the combination therapy generated a strong and durable specific anti-tumor immune response, although the immune response alone was unable to control the tumor growth after the termination of the therapy. This approach represents a promising therapy to improve the clinical outcomes for tumors sensitive to both dsRNA and gemcitabine.

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    • "As controls, tumorbearing mice were injected with sterile mannitol solution (5%) or gemcitabine HCl dissolved in mannitol solution. To make sure that the same molar amount of gemcitabine was injected, the doses of the gemcitabine HCl and GemC18 were 0.566 mg and 1 mg per mouse, respectively (Le et al., 2008; Pratesi et al., 2005). To evaluate the anti-tumor activity of the nanoparticles when injected peritumorally, PEG-GemC18-NPs or GemC18-NPs (0.25 mg of GemC18 in 50 μL) were injected three times per week for a total of 5 times peritumorally around TC-1 tumors, starting when the tumors reached 5 mm in diameter. "
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