Localized irradiation of tumors prior to synthetic dsRNA therapy enhanced the resultant anti-tumor activity

Background and purpose: 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. Materials and 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. (C) 2008 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 90 (2009) 273-279