Dual Therapeutic Efficacy of Vinblastine as a Unique Chemotherapeutic Agent Capable of Inducing Dendritic Cell Maturation

摘要: Our recent unbiased functional screen of 54 chemotherapeutic drugs unveiled striking heterogeneity in their effects on dendritic cells (DC). Most notably, vinblastine (VBL) was found to induce phenotypic and maturation DCs vitro. Here, we sought determine whether VBL exhibits "dual" therapeutic efficacy living animals by directly killing tumor boosting host immunity via DC maturation. Local injection a low dose into the skin C57BL/6 mice induced situ epidermal Langerhans cells. When coinjected with model antigen, ovalbumin (OVA), enhanced OVA-specific cellular humoral immune responses. injected OVA cDNA-transduced E.G7 tumors, augmented clonal expansion OVA-reactive CD8 T CTL activities. In B16 melanoma model, intratumor apoptosis cells, tumor-infiltrating DCs, significant Although complete clearance never achieved, growth kinetic markedly reduced injection. Importantly, same treatment far less efficacious immunocompromised severe combined immunodeficient mice, indicating requirement intact immunity. results introduce new concept that may be used design "immunostimulatory" chemotherapy regimens.