Antitumor Effect of Anti-Brain Derived Neurotrophic Factor Monoclonal Antibody in Human Multiple Myeloma Xenograft Animal Model

This study was aimed to further explore whether brain derived neurotrophic factor (BDNF) pathway is a potential therapeutic target in multiple myeloma (MM) and whether anti-BDNF monoclonal antibody can prevent the development of this disease. The in vivo antitumor effect of anti-BDNF monoclonal antibody (McAb) on a human myeloma xenograft animal model was evaluated. The model of xenograft tumors was established in the nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice by subcutaneous injection of human myeloma cell line RPM18226. The antibodies were injected intraperitoneally at a dose of 20 μg/mouse at day 1, 2, 3 after inoculation or at a dose of 100 μg/mouse once a week after tumors were detected. The microvascular densities in tumors were analyzed by immunohistochemistry study. The effect of anti-BDNF McAb on the proliferation of RPM18226 cells in vitro and on endothelial cells network formation in the co-culture system were determined by using a 3H-thymidine incorporation assay and a Matrigel network formation assay, respectively. The results showed that multiple injections of anti-BDNF McAb reduced the tumor size, decreased the microvascular density and significantly prolonged tumor-free time and survival time. Moreover, the proliferation of RPM18226 cells was inhibited in vitro by anti-BDNF McAb, but not by the control IgG. Anti-BDNF McAb also inhibited RPM18226-induced network formation in endothelial cells in vitro. It is concluded that anti-BDNF monoclonal antibody can inhibit cell growth and angiogenesis in subcutaneous plasmacytoma.