Polyclonal antibodies to xenogeneic endothelial cells induce apoptosis and block support of tumor growth in mice.
In this study, we demonstrate that vaccination of rabbits with murine endothelial cells yields polyclonal immunoglobulin (IgG) with potent antiangiogenic activity. The mechanism of this response appears to be through apoptosis of endothelial cells in vitro. Induction of polyclonal IgG in a xenogeneic host may be useful in passive immunotherapy of a variety of cancers. In fact, the antibody showed antitumor activity in three mouse tumor models (murine B16F10 melanoma, murine SVR angiosarcoma, and human DLD-1 colorectal adenocarcinoma). The polyclonal antibody generated here demonstrated utility in radioimaging of tumors in vivo, using positron emission tomography (PET) imaging, and suggested an antitumor effect in vivo. The results suggest that the antitumor effect in vivo may be related to antiangiogenic effects. Furthermore, anti-endothelial cell antibodies such as these could be useful reagents in isolating specific targets that comprise and induce the antiangiogenic effect.
Scappaticci
F A
FA
Department of Pathology, Stanford University Medical Center, 269 Campus Drive CCSR 3220, Stanford, CA 94305-5332, USA.
Contreras
A
A
Boswell
C A
CA
Lewis
J S
JS
Nolan
G
G
D016475:3T3 Cells; D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000627:therapeutic use*; D002455:Cell Division / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D004730:Endothelium, Vascular / Q000637:transplantation*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000473:pathology / Q000628:therapy; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000473:pathology / Q000628:therapy; D008546:Melanoma, Experimental / Q000098:blood supply / Q000473:pathology / Q000628:therapy; D051379:Mice; D009389:Neovascularization, Pathologic / Q000276:immunology; D011817:Rabbits; D014183:Transplantation, Heterologous / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins
D000906:Antibodies; D007074:Immunoglobulin G