Antitumor effect of anti-brain derived neurotrophic factor monoclonal antibody in human multiple myeloma xenograft animal model.
- Author:
Ya-Dan WANG
1
;
Yu HU
;
Jin HUANG
;
Lu ZHANG
;
Chun-Yan SUN
Author Information
1. Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Antibodies, Monoclonal;
therapeutic use;
Brain-Derived Neurotrophic Factor;
immunology;
Cell Line, Tumor;
Humans;
Male;
Mice;
Mice, SCID;
Multiple Myeloma;
drug therapy;
metabolism;
pathology;
Neoplasms, Plasma Cell;
drug therapy;
Xenograft Model Antitumor Assays
- From:
Journal of Experimental Hematology
2008;16(5):1069-1072
- CountryChina
- Language:English
-
Abstract:
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 RPMI8226. The antibodies were injected intraperitoneally at a dose of 20 microg/mouse at day 1, 2, 3 after inoculation or at a dose of 100 microg/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 RPMI8226 cells in vitro and on endothelial cells network formation in the co-culture system were determined by using a (3)H-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 RPMI8226 cells was inhibited in vitro by anti-BDNF McAb, but not by the control IgG. Anti-BDNF McAb also inhibited RPMI8226-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.
