Localized irradiation of tumors prior to synthetic dsRNA therapy enhanced the resultant anti-tumor activity.
OBJECTIVE
Despite the potent tumoricidal activity of the synthetic dsRNA in culture, its in vivo anti-tumor activity has proven to be limited. We sought to devise and validate a new strategy to improve the in vivo anti-tumor activity by integrating localized irradiation into dsRNA therapy.


METHODS
Using a mouse lung cancer model and a mouse melanoma model in immuno-competent mice or athymic nude mice, we evaluated the combined anti-tumor activity using a synthetic dsRNA, polyinosine-cytosine (poly(I:C)).


RESULTS
Localized irradiation of tumors prior to the poly(I:C) therapy significantly delayed the tumor growth as compared to monotherapies using the radiation or poly(I:C) alone. The poly(I:C) enhanced the tumor response to radiation with a dose modification factor as large as 20. The combined effect was synergistic only in immuno-competent mice with highly immunogenic tumors. The anti-tumor activity of the combination therapy was significantly impaired when the type I interferons in the mice were neutralized.


CONCLUSIONS
This combination modality may represent a promising approach to exploit synthetic dsRNA in cancer therapy and to enhance tumor response to radiation. T cell-mediated immunity was likely responsible for the combined synergistic effect. Type I interferons contributed significantly to the combined anti-tumor activity.
Le
Uyen M
UM
Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR 97331, USA.
Kaurin
Darryl G L
DG
Sloat
Brian R
BR
Yanasarn
Nijaporn
N
Cui
Zhengrong
Z
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005260:Female; D007121:Immunocompetence; D007369:Interferon Inducers / Q000627:therapeutic use*; D007370:Interferon Type I / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000532:radiotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011070:Poly I-C / Q000627:therapeutic use*; D012330:RNA, Double-Stranded / Q000138:chemical synthesis / Q000627:therapeutic use*; D018714:Radiotherapy, Adjuvant
D000970:Antineoplastic Agents; D007369:Interferon Inducers; D007370:Interferon Type I; D012330:RNA, Double-Stranded; D011070:Poly I-C