Monoclonal antibodies specific to BST-2 accumulate on lymphoma blood vessels and inhibit lymphoma growth in vivo. (A) A monoclonal rat anti–BST-2 antibody (clone 927) was intravenously injected into BALB/c mice bearing systemic or subcutaneous A20 lymphomas. Tumors and normal liver were excised 6 hours after injection, sectioned, and examined for the presence of rat IgG using donkey anti–rat Alexa Fluor 488 (green). Endothelial cells (CD31) were outlined in red. Although the anti–BST-2 antibody efficiently homed to lymphoma neovasculature in vivo (solid arrowheads), an isotype-matched control IgG did not accumulate on lymphoma blood vessels under identical experimental conditions. The hollow arrowhead indicates a BST-2–negative vessel that was most probably not perfused in vivo. Scale bars represent 50 μm. Slides were viewed with an LSM510 Meta confocal microscope (Carl Zeiss) using 10×/0.45 W and 40×/1.2 W water objectives and Fluorescent Mounting Medium (Dako). Images were acquired with the LSM510 Meta confocal laser scanning microscope and software provided by the manufacturer (Carl Zeiss). Images were manipulated using ImageJ software, Version 1.42q (available at http://rsb.info.nih.gov/ij/). (B) Tumor growth curves of A20 lymphomas subcutaneously implanted into BALB/c mice, treated with anti–BST-2 antibody 129c (5 mg/kg, 5 mice), anti–BST-2 antibody 927 (5 mg/kg, 5 mice), or isotype-matched control antibody (5 mg/kg, 4 mice). Treatment was administered intravenous once weekly for a period of 3 weeks. Both BST-2 antibodies significantly inhibited lymphoma growth (P = .014 and P = .008, respectively). (C) The lack of weight loss in each animal indicates that anti–BST-2 therapy was well tolerated.