Issue 6, 2022

Homogeneous antibody–angiopep 2 conjugates for effective brain targeting


Antibody-based therapy has shown great success in the treatment of many diseases, including cancers. While antibodies and antibody–drug conjugates (ADCs) have also been evaluated for central nervous system (CNS) disorders as well as brain tumors, their therapeutic efficacy can be substantially limited due to low permeability across the blood–brain barrier (BBB). Thus, improving BBB permeability of therapeutic antibodies is critical in establishing this drug class as a reliable clinical option for CNS diseases. Here, we report that, compared with a conventional heterogeneous conjugation, homogeneous conjugation of the synthetic BBB shuttle peptide angiopep-2 (Ang2) to a monoclonal antibody (mAb) provides improved binding affinity for brain microvascular endothelial cells in vitro and accumulation into normal brain tissues in vivo. In a mouse model, we also demonstrate that the homogeneous anti-EGFR mAb–Ang2 conjugate administered intravenously efficiently accumulates in intracranial tumors. These findings suggest that homogeneous conjugation of BBB shuttle peptides such as Ang2 is a promising approach to enhancing the therapeutic efficacy of antibody agents for CNS diseases.

Graphical abstract: Homogeneous antibody–angiopep 2 conjugates for effective brain targeting

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Article information

Article type
05 Nov 2021
27 Dec 2021
First published
26 Jan 2022
This article is Open Access
Creative Commons BY license

RSC Adv., 2022,12, 3359-3364

Homogeneous antibody–angiopep 2 conjugates for effective brain targeting

Y. Anami, W. Xiong, A. Yamaguchi, C. M. Yamazaki, N. Zhang, Z. An and K. Tsuchikama, RSC Adv., 2022, 12, 3359 DOI: 10.1039/D1RA08131D

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