A critical evaluation of the tumor-targeting properties of bispecific antibodies based on quantitative biodistribution data

• Published in: Protein engineering, design and selection Vol. 25; no. 12; pp. 851 - 854
• Main Authors: Hemmerle, Teresa, Wulhfard, Sarah, Neri, Dario
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.12.2012
• Subjects: Alternative splicing; Animal models; Animals; Antibodies, Bispecific - biosynthesis; Antibodies, Bispecific - immunology; Antibodies, Bispecific - pharmacokinetics; Antibodies, Monoclonal - genetics; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - metabolism; Bispecific antibodies; CD86 antigen; Cell Line, Tumor; Data processing; Fibronectin; Fibronectins - genetics; Fibronectins - metabolism; HEK293 Cells; Humans; imaging; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Tissue Distribution; Tumors; bispecific antibody; vascular targeting; oncofetal fibronectin; co-stimulatory molecule B7.2; antibody F8
• ISSN: 1741-0126; 1741-0134
• DOI: 10.1093/protein/gzs061

Bispecific and bifunctional antibodies are attracting considerable interest as innovative anti-cancer therapeutics, but their ability to selectively localize at the tumor site has rarely been studied by quantitative biodistribution studies in immunocompetent animal models or in patients. Here, we describe the production of a novel bifunctional antibody, consisting of the F8 antibody (specific to the alternatively spliced EDA domain of fibronectin) fused to the extracellular portion of CD86 (co-stimulatory molecule B7.2). However, the fusion molecule was unable to target tumors in vivo. These data suggest that bispecific antibodies do not always localize on tumors and should therefore be characterized by imaging or biodistribution studies.