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A bivalent, bispecific Dab-Fc antibody molecule for dual targeting of HER2 and HER3 by Alexander Rau; Katharina Kocher; Mirjam Rommel; Lennart Kühl; Maximilian Albrecht; Hannes Gotthard; Nadine Aschmoneit; Bettina Noll; Monilola A. Olayioye; Roland E. Kontermann; Oliver Seifert is a Medicine article available to read on EtoBox.

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## ABSTRACT Dual targeting of surface receptors with bispecific antibodies is attracting increasing interest in cancer therapy. Here, we present a novel bivalent and bispecific antagonistic molecule (Dab-Fc) targeting human epidermal growth factors 2 and 3 (HER2 and HER3) derived from the Db-Ig platform, which was developed for the generation of multivalent and multispecific antibody molecules. Dab-Fc comprises the variable domains of the anti-HER2 antibody trastuzumab and the anti-HER3 antibody 3–43 assembled into a diabody-like structure stabilized by C~H~1 and C~L~ domains and further fused to a human γ1 Fc region. The resulting Dab-Fc 2 × 3 molecule retained unhindered binding to both antigens and was able to bind both antigens sequentially. In cellular experiments, the Dab-Fc 2 × 3 molecule strongly bound to different tumor cell lines expressing HER2 and HER3 and was efficiently internalized. This was associated with potent inhibition of the proliferation and migration of these tumor cell lines. Furthermore, IgG-like pharmacokinetics and anti-tumoral activity were demonstrated in a xenograft tumor model of the gastric cancer cell-line NCI-N87. These results illustrate the suit

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Author

Alexander Rau; Katharina Kocher; Mirjam Rommel; Lennart Kühl; Maximilian Albrecht; Hannes Gotthard; Nadine Aschmoneit; Bettina Noll; Monilola A. Olayioye; Roland E. Kontermann; Oliver Seifert

Publisher

Informa UK Limited

Published

2021

Language

EN

Field

Medicine (Life Sciences)