title: Biodistribution studies with tumor-targeting bispecific antibodies reveal selective accumulation at the tumor site.
abstract: Bispecific antibodies are proteins that bind two different antigens and may retarget immune cells with a binding moiety specific for a leukocyte marker. A binding event in blood could in principle prevent antibody extravasation and accumulation at the site of disease. In this study, we produced and characterized two tetravalent bispecific antibodies that bind with high affinity to the alternatively-spliced EDB domain of fibronectin, a tumor-associated antigen. The bispecific antibodies simultaneously engaged the cognate antigens (murine T cell co-receptor CD3 and hen egg lysozyme) and selectively accumulated on murine tumors in vivo. The results, which were in agreement with predictions based on pharmacokinetic modeling and antibody binding characteristics, confirmed that bispecific antibodies can reach abluminal targets without being blocked by peripheral blood leukocytes.
authors.affiliation: Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology ETH Zürich, Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: List
authors.forename: Dario
authors.initials: D
authors.lastname: Neri
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D018033:Antibodies, Bispecific / Q000378:metabolism*; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000276:immunology; D017252:CD3 Complex / Q000378:metabolism; D054278:Embryonal Carcinoma Stem Cells; D005353:Fibronectins / Q000235:genetics / Q000276:immunology; D006801:Humans; D051379:Mice; D015202:Protein Engineering; D017434:Protein Structure, Tertiary / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D018243:Teratocarcinoma / Q000276:immunology / Q000628:therapy*
chemical_list: D018033:Antibodies, Bispecific; D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm; D017252:CD3 Complex; D005353:Fibronectins; D011948:Receptors, Antigen, T-Cell