Diagnostic and therapeutic applications of recombinant antibodies: targeting the extra-domain B of fibronectin, a marker of tumor angiogenesis.
Angiogenesis, the sprouting of new blood vessels from preexisting ones, is a phenomenon associated to several human pathologies, including different potentially blinding ocular disorders, rheumatoid arthritis, and cancer. Indeed, ongoing angiogenesis is a characteristic feature of the majority of aggressive solid tumors, and is also a pre-requisite for the progression towards the metastatic phenotype. One established marker of angiogenesis is represented by an isoform of the oncofoetal fibronectin (FN), containing an additional domain inserted by alternative splicing of the FN pre-mRNA and called extra-domain B (ED-B). This isoform has been found to be present almost exclusively in the modified extra-cellular matrix surrounding newly-formed blood vessels in tumors (and other animal models of ocular pathologies), being completely absent from the normal vasculature in adult organs. This article reviews the recombinant antibodies raised against ED-B and the different methodologies used for the generation of these antibodies. Moreover, new diagnostic and therapeutic applications based on the delivery of bioactive molecules to tumor blood vessels by means of ED-B targeting will be discussed.
Ebbinghaus
Christina
C
Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Scheuermann
Jörg
J
Neri
Dario
D
Elia
Giuliano
G
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism
D000906:Antibodies; D014408:Biomarkers, Tumor; D005353:Fibronectins; D011994:Recombinant Proteins