Antibody-directed targeting of the vasculature of solid tumors.
An attractive strategy for the therapy of carcinomas and other solid tumors would be to target cytotoxic agents or host immune effectors to the endothelial cells of the tumor vasculature rather than to the tumor cells themselves. The key advantage of this approach is that the endothelial cells are freely accessible through the blood whereas the tumor cells are, for the most part, inaccessible. Also, endothelial cells are similar in different tumors, making it feasible to develop a single reagent for treating numerous types of cancer. In this chapter, we review progress in this "vascular targeting" approach, from the validation of the concept in a mouse model to the characterization of the TEC-11 antibody against endoglin, an endothelial cell proliferation marker that is upregulated on endothelial cells in miscellaneous human solid tumors. In addition, we review other tumor endothelial cell markers that are candidates for vascular targeting in man.
University of Texas Southwestern Medical Center, Dallas 75235, USA.
P E
PE
Thorpe
F J
FJ
Burrows
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology; D002277:Carcinoma / Q000098:blood supply* / Q000188:drug therapy; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy*
D000911:Antibodies, Monoclonal; D000922:Immunotoxins