Antibody-based targeting of the tumor vasculature.
Conventional cytotoxic therapies of cancer often suffer from a lack of specificity, leading to a poor therapeutic index and considerable toxicities to normal organs. An elegant way to overcome the disadvantages of conventional tumor therapy is the selective delivery of therapeutics to the tumor site by their conjugation to a carrier molecule specific for a tumor-associated molecular marker. Markers expressed on the tumor's vasculature represent particularly attractive targets for a site-specific pharmacodelivery due to their inherent accessibility for blood-borne agents and the various therapeutic options that they allow, ranging from intraluminal blood coagulation to the recruitment of immune cells. In this review, we will outline advances in the preclinical and clinical evaluation of antibody-based vascular targeting agents, describe technologies for the discovery of novel vascular targets and discuss future prospects for vascular targeting applications.
Schliemann
Christoph
C
Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zürich, Wolfgang-Pauli-Strasse 10, HCI G396, 8093 Zürich, Switzerland.
Neri
Dario
D
D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000032:analysis; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000187:drug effects; D009369:Neoplasms / Q000098:blood supply* / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor; D008565:Membrane Proteins