Anti-tumoral, Anti-angiogenic and Anti-metastatic Efficacy of a Tetravalent Bispecific Antibody (TAvi6) Targeting VEGF-A and Angiopoietin-2

Overview

Journal MAbs

Specialty Allergy & Immunology

Date 2016 Feb 12

PMID 26864324

Citations 12

Authors

Werner Scheuer

Markus Thomas

Petra Hanke

Johannes Sam

Franz Osl

Diana Weininger

Monika Baehner

Stefan Seeber

Hubert Kettenberger

Jurgen Schanzer

Ulrich Brinkmann

K Michael Weidner

Jorg Regula

Christian Klein

Affiliations

Soon will be listed here.

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.

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