Work

Influence of the Binding Valency of Anti-HER2 Biparatopic Antibodies on Biodistribution in an SK-OV-3 Tumor Xenograft Model

Year: 2026

Type: article

Abstract: Biparatopic antibodies (BpAbs) are an attractive format of engineered therapeutic antibodies that bind to two distinct epitopes of a single antigen. Accelerated cell internalization is anticipated in many developmental campaigns, and both bivalent and tetravalent forms have been developed for this purpose. However, their pharmacokinetic properties have not been understood systematically; thus, optimization approaches for BpAbs have been limited. In this study, we conducted a comparative biodistribution analysis of bivalent and tetravalent BpAbs using the same variable fragments. Two different pairs of epitopes of human epidermal growth factor receptor 2 (HER2) were targeted, and their distribution was evaluated in a tumor xenograft model by 111 In-labeling. Bivalent BpAbs showed higher accumulation in tumors than tetravalent BpAbs in both cases. However, epitope-dependent differences in biodistribution did not correlate with those of the original monoclonal antibodies. In addition, cell internalization during the early stages of incubation was higher for tetravalent BpAbs. These results suggest the advantage of bivalent BpAbs over tetravalent BpAbs in pharmacokinetics; however, the design may require optimization depending on the mechanism of action of the BpAb of interest.

Source: Molecular Pharmaceutics

DOI: 10.1021/acs.molpharmaceut.5c01515

Authors: Hiroki Akiba, Kazuma Nakashima, Takayoshi Ichinose, Hiroyuki Watanabe, Masahiro Ono

Institution: Kyoto University

Language: English

Topic: Monoclonal and Polyclonal Antibodies Research

Subfield: Radiology, Nuclear Medicine and Imaging

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funder: Japan Agency for Medical Research and Development