[Monoclonal antibody against brain derived neurotrophic factor inhibits myeloma growth and angiogenesis in the xenograft NOD/SCID animal model].
OBJECTIVE
To evaluate the in vivo antitumor effect of anti-brain derived neurotrophic factor (BDNF) monoclonal antibody (MoAb) on a human myeloma xenograft animal model.


METHODS
The xenograft tumor model was established in the nonobese diabetic/severe combined immunodeficiency (NOD/ SCID) mice by subcutaneous injection of human myeloma cell line RPMI 8226. The antibodies were injected intraperitoneally at a dose of 20 microg/mouse at day 1, day 2, day 3 after tumor cell inoculation or at a dose of 100 microg/mouse once a week after tumors were developed. The histologic and cytologic examination were performed to confirm the development of plasmacytomas. The microvascular densities (MVD) in tumors were analyzed by immunohistochemistry. The effect of anti-BDNF MoAb on the proliferation of RPMI 8226 cells in vitro and on endothelial cell network formation in the co-culture system were determined by 3H-thymidine incorporation assay and Matrigel network formation assay, respectively.


RESULTS
The xenograft NOD/SCID animal model had high capacity for growth of RPMI 8226 subcutaneous tumors and presented pathologic features of plasmacytomas. After subcutaneous injection of RPMI 8226 cells, all mice developed localized tumors in (20 +/- 2) d. On 20 microg anti-BDNF MoAb 3 consecutive treatment, the mean tumor-free time was extended to (30 +/- 6) d and survival was significantly prolonged compared with IgG-treated group [(57 +/- 7) d vs (48 +/- 4) d, P < 0.05]. When mice died naturally, the tumors size in anti-BDNF MoAb treated ones was also reduced compared with control group [(157.9 +/- 21.6) mm3 vs (405.5 +/- 35.2) mm3, P < 0.05]. When the antibody treatment (100 microg/mouse) underwent from 27 th to 60 day once a week after tumor inoculation, the local tumor growth was inhibited partially and necrosis and infiltration were observed in the tumors. The median MVD in the antibody-treated mice (100 microg/mouse) was 11 vessels/0.216 mm2. The IgG treated mice had no decrease in MVD of subcutaneous tumors compared with untreated mice. In vitro, anti-BDNF MoAb (1.5 microg/ml) significantly but partially inhibited HUVEC network formation induced by RPMI 8226 (68.2% reduction) and significantly inhibited RPMI 8226 proliferation, too. The IgG (1.5 microg/ml) treated mice had no significant effect on both of two assays.


CONCLUSIONS
Anti-BDNF monoclonal antibody could inhibit growth and angiogenesis in subcutaneous myeloma tumors. BDNF is a potential therapeutic target in MM.
Wang
Ya-dan
YD
Institution of Hematology, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Hu
Yu
Y
Zhang
Lu
L
Huang
Jing
J
Sun
Chun-yan
CY
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D019208:Brain-Derived Neurotrophic Factor