Anti-tumoral, anti-angiogenic and anti-metastatic efficacy of a tetravalent bispecific antibody (TAvi6) targeting VEGF-A and angiopoietin-2. Issue 3 (2nd April 2016)

• Record Type: Journal Article
• Authors: Scheuer, Werner; Thomas, Markus; Hanke, Petra; Sam, Johannes; Osl, Franz; Weininger, Diana; Baehner, Monika; Seeber, Stefan; Kettenberger, Hubert; Schanzer, Jürgen; Brinkmann, Ulrich; Weidner, K. Michael; Regula, Jörg; Klein, Christian
• Is Part Of: MAbs. Volume 8:Issue 3(2016)
• Page Start: 562
• Page End: 573
• Publication Date: 2016-04-02
• Subjects: Angiopoietin-2; bispecific; BsAb; scFv; VEGF-A; Monoclonal antibodies -- Therapeutic use -- Periodicals; Monoclonal antibodies -- Periodicals; Antibodies, Monoclonal -- Periodicals; 616.0798
• DOI: 10.1080/19420862.2016.1147640
• Languages: English
• ISSNs: 1942-0862

Abstract

ABSTRACT: Vascular endothelial growth factor (VEGF)-A blockade has been validated clinically as a treatment for human cancers. Angiopoietin-2 (Ang-2) is a key regulator of blood vessel remodeling and maturation. In tumors, Ang-2 is up-regulated and an unfavorable prognostic factor. Recent data demonstrated that Ang-2 inhibition mediates anti-tumoral effects. We generated a tetravalent bispecific antibody (Ang-2-VEGF-TAvi6) targeting VEGF-A with 2 arms based on bevacizumab (Avastin®), and targeting Ang-2 with 2 arms based on a novel anti-Ang-2 antibody (LC06). The two Ang-2-targeting single-chain variable fragments are disulfide-stabilized and fused to the C-terminus of the heavy chain of bevacizumab. Treatment with Ang-2-VEGF-A-TAvi6 led to a complete abrogation of angiogenesis in the cornea micropocket assay. Metastatic spread and tumor growth of subcutaneous, orthotopic and anti-VEGF-A resistant tumors were also efficiently inhibited. These data further establish Ang-2-VEGF bispecific antibodies as a promising anti-angiogenic, anti-metastatic and anti-tumor agent for the treatment of cancer.