ArticleFrontiers in immunology2025
Engineering HER2-targeted biparatopic antibodies to promote receptor internalization and restore antitumor efficacy.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
HER2 is a well-established oncogenic driver in breast, gastric, and other solid tumors. While HER2-targeted therapies such as trastuzumab and pertuzumab have improved clinical outcomes, resistance, particularly to trastuzumab, remains a major therapeutic challenge. Here, we engineered two IgG-VHH biparatopic antibodies (bpAbs), A9B5-Bs-5 and A9B5-Bs-7, incorporating an ECD I-binding nanobody A9B5 with the IgG scaffolds. These bpAbs target non-overlapping epitopes on the HER2 extracellular domain, promoting rapid receptor internalization and demonstrating superior antitumor activity compared to the trastuzumab and pertuzumab combination in trastuzumab-resistant tumor cells. Structural modeling suggests that both bpAbs engage HER2 in a
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