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Tumor chemo-immunotherapy using gemcitabine and a synthetic dsRNA.
|Title||Tumor chemo-immunotherapy using gemcitabine and a synthetic dsRNA.|
|Publication Type||Journal Article|
|Year of Publication||2008|
|Authors||Le UM, Yanasarn N, Löhr CV, Fischer KA, Cui Z|
|Journal||Cancer biology & therapy|
|Date Published||2008 Mar|
|Keywords||Adjuvants, Immunologic, Antimetabolites, Antineoplastic, Apoptosis, Cell Line, Tumor, Dendritic Cells, Dose-Response Relationship, Drug, Humans, Immunosuppressive Agents, Poly I-C, RNA, Double-Stranded, Toll-Like Receptors|
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.
|Alternate Journal||Cancer Biol. Ther.|