Synergistic effect of metronomic dosing of cyclophosphamide combined with specific antitumor immunotherapy in a murine melanoma model.

摘要: Immunotherapy could be combined with conventional chemotherapeutic modalities aimed at reducing tumor burden. Such combination therapy may most useful when "metronomic" doses of antineoplastic drugs are used, thereby potentially avoiding some the immunosuppressive effects these drugs. Recent studies have shown that can exploited for antiangiogenic capacities, a strategy requires to administered regular intervals. We therefore investigated whether such metronomic alkylating agent cyclophosphamide (CTX) effectively immunotherapy eliciting tumor-reactive CTLs. An immunization protocol using injection recombinant DNA followed by modified vaccinia virus Ankara strain was used initiate specific CTL response in mice capable providing resistance challenge murine melanoma B16.F10. Combining this immunotherapeutic regime delivery CTX resulted antitumor activity dramatically enhanced over either treatment alone and also significantly greater than combining maximum tolerated dose regime. Whereas both did cause deletion proliferating tumor-specific CTLs blood, occurred slower kinetics schedule. Further analysis showed not delete cells low expression CD43, "memory" phenotype, maintained potent restimulatory capacity. The well suited clinical management cancer.