Intermittent chemotherapy can retain the therapeutic potential of anti-CD137 antibody during the late tumor-bearing state.
Bottom Line: Although a significant antitumor effect was observed when local anti-CD137 mAb therapy (5 μg) was started early in the tumor-bearing stage (day 10), no therapeutic efficacy was observed when the mAb therapy was started at a later tumor-bearing stage (day 17).In a bilateral tumor inoculation model, this combination therapy achieved systemic therapeutic effects and suppressed the growth of mAb-untreated tumors.These results suggest that intermittent immunochemotherapy using CP and GEM could retain the therapeutic potential of anti-CD137 mAb that is normally impaired during the late tumor-bearing stage.
Affiliation: Department of Experimental Animals, Center for Integrated Research in Science, Shimane University, Izumo, Japan.Show MeSH
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Mentions: To investigate why the therapeutic efficacy of local anti-CD137 mAb therapy was lost at the late tumor-bearing stage, we quantified the number of tumor-infiltrating immune cells (Fig.2a). The percentage of CD45+ immune cells, particularly CD11b+ Gr-1high/low MDSC, in the tumor tissues increased significantly 13 days after tumor inoculation. Although the percentage of CD4+ T cells in TIL decreased gradually, the number of CD8+ T cells increased slightly. In addition, the percentage of Tregs increased in TIL on days 13 and 18 after tumor inoculation. However, given the low percentages of total CD4+ T cells in TIL, MDSC appeared to be responsible for the impaired efficacy of local anti-CD137 mAb therapy in the late tumor-bearing stage. Representative results of the number of CD45+ immune cells and MDSC on days 10 and 18 after tumor inoculation are shown in Figure2(b).
Affiliation: Department of Experimental Animals, Center for Integrated Research in Science, Shimane University, Izumo, Japan.