Tumor chemo-immunotherapy using gemcitabine and a synthetic dsRNA.
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.
Le
Uyen M
UM
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon 97331, USA.
Yanasarn
Nijaporn
N
Löhr
Christiane V
CV
Fischer
Kay A
KA
Cui
Zhengrong
Z
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D011070:Poly I-C / Q000627:therapeutic use*; D012330:RNA, Double-Stranded / Q000138:chemical synthesis / Q000627:therapeutic use*; D051193:Toll-Like Receptors / Q000187:drug effects / Q000502:physiology
D000276:Adjuvants, Immunologic; D000964:Antimetabolites, Antineoplastic; D007166:Immunosuppressive Agents; D012330:RNA, Double-Stranded; D051193:Toll-Like Receptors; D011070:Poly I-C