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: We first examined the expression of CD137 on draining LN cells, spleen cells and tumor-infiltrating lymphocytes (TIL) of CT26-bearing mice 12 days after tumor inoculation. Both CD4+ and CD8+ T cells in TIL, but not draining LN or splenic cells, were weakly positive for CD137 (Fig.1a), consistent with a previous report.10 We next examined the antitumor effects induced by the intratumoral delivery of low-dose (5 μg) anti-CD137 mAb. The i.t. injection with anti-CD137 mAb on days 10, 12 and 14 after tumor inoculation suppressed tumor growth significantly compared with the injection of control rat IgG (Fig.1b). This antitumor effect was T-cell-dependent because no antitumor effect was observed in CT26-bearing nude mice (Fig.1c). We also assessed whether the anti-CD137 mAb therapy was effective when started at a later tumor-bearing stage. Although the tumor in one mouse regressed and another mouse showed continuous suppression of the tumor growth, i.t. injections of anti-CD137 mAb on days 17, 19 and 21 were not effective (Fig.1d).
Affiliation: Department of Experimental Animals, Center for Integrated Research in Science, Shimane University, Izumo, Japan.