Eradication of large solid tumors in mice with an immunotoxin directed against tumor vasculature.
Antibody-based therapy of solid tumors has met with limited success, chiefly because solid tumors are relatively impermeable to macromolecules. This problem could be circumvented by attacking the readily accessible endothelial cells of the tumor vascular bed. We have developed a model to test this "vascular targeting" approach in which cytokine gene transfection of the tumor cells causes them to induce an experimental marker selectively on tumor vascular endothelium. An anti-tumor endothelial cell immunotoxin caused complete occlusion of the tumor vasculature and dramatic regressions of large solid tumors. By contrast, a conventional anti-tumor cell immunotoxin of equivalent in vitro potency produced only minor, transient antitumor effects but, when combined, the two immunotoxins induced permanent complete remissions in over half of the animals. These experiments indicate that immunotoxins directed against recently described markers on vascular endothelial cells in human tumors could provide a general treatment for solid tumors in humans.
Burrows
F J
FJ
Cancer Immunobiology Center, University of Texas Southwestern Medical Center, Dallas 75235-8576.
Thorpe
P E
PE
D000818:Animals; D000911:Antibodies, Monoclonal; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004727:Endothelium / Q000166:cytology* / Q000187:drug effects; D000922:Immunotoxins / Q000627:therapeutic use* / Q000633:toxicity; D007371:Interferon-gamma / Q000633:toxicity*; D051379:Mice; D008805:Mice, Inbred A; D008819:Mice, Nude; D009389:Neovascularization, Pathologic; D009447:Neuroblastoma / Q000098:blood supply* / Q000628:therapy*; D011994:Recombinant Proteins; D012276:Ricin / Q000627:therapeutic use* / Q000633:toxicity; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D011994:Recombinant Proteins; D007371:Interferon-gamma; D012276:Ricin