Combined Treatment of Murine Fibrosarcoma with Chemotherapy (Paclitaxel), Radiotherapy, and Intratumoral Injection of Dendritic Cells
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Background: New antitumor therapeutic strategies aim tocombine different approaches that are able to inducetumor-specific effector and memory T cell responses thatmight control tumor growth. Dendritic cells (DCs) havethe capacity to induce antigen-specific cytotoxic T lymphocytes. We have previously shown that the combinedtreatment of paclitaxel chemotherapy (Chemo) and injectionof DCs led to complete tumor regression. Objective:The goal of this study was to evaluate synergistic antitumoreffect of a triple combination treatment comprisingradiotherapy, paclitaxel Chemo and intratumoral injectionof syngeneic bone marrow-derived DCs on murinefibrosarcoma, compared to other single or double combinationtreatments. Methods: For the murine fibrosarcomamodel, naïve C57BL/6 mice were inoculated intradermallywith 2×103 MCA102 cells in the right upper flank. Mice were assigned to five groups (untreatedcontrol, RTalone, RT+Chemo, RT+DC, and RT+Chemo+DC), witheight mice in each group. In vitro cytotoxicity assays wereperformed to assess the immune activity. The persistenceof tumor-specific immunity was determined by secondtumor challenge in mice with complete tumor regression. Results: The triple combination treatment showed asignificantly enhanced therapeutic efficacy by decreasingtumor size and inducing complete tumor regression,resulting in a cure of 50% of mice. The results of in vitrocytotoxicity assays and the second tumor challengeexperiment strongly indicated the induction of a tumor-specific cytotoxic T lymphocyte response and acquisitionof prolonged tumor immunity. Conclusion: Thesefindings suggest that the triple combination treatment canbe a promising strategy for the treatment of murinefibrosarcoma.
Abstract
Background: New antitumor therapeutic strategies aim tocombine different approaches that are able to inducetumor-specific effector and memory T cell responses thatmight control tumor growth. Dendritic cells (DCs) havethe capacity to induce antigen-specific cytotoxic T lymphocytes. We have previously shown that the combinedtreatment of paclitaxel chemotherapy (Chemo) and injectionof DCs led to complete tumor regression. Objective:The goal of this study was to evaluate synergistic antitumoreffect of a triple combination treatment comprisingradiotherapy, paclitaxel Chemo and intratumoral injectionof syngeneic bone marrow-derived DCs on murinefibrosarcoma, compared to other single or double combinationtreatments. Methods: For the murine fibrosarcomamodel, naïve C57BL/6 mice were inoculated intradermallywith 2×103 MCA102 cells in the right upper flank. Mice were assigned to five groups (untreatedcontrol, RTalone, RT+Chemo, RT+DC, and RT+Chemo+DC), witheight mice in each group. In vitro cytotoxicity assays wereperformed to assess the immune activity. The persistenceof tumor-specific immunity was determined by secondtumor challenge in mice with complete tumor regression. Results: The triple combination treatment showed asignificantly enhanced therapeutic efficacy by decreasingtumor size and inducing complete tumor regression,resulting in a cure of 50% of mice. The results of in vitrocytotoxicity assays and the second tumor challengeexperiment strongly indicated the induction of a tumor-specific cytotoxic T lymphocyte response and acquisitionof prolonged tumor immunity. Conclusion: Thesefindings suggest that the triple combination treatment canbe a promising strategy for the treatment of murinefibrosarcoma.
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