Molecular Mechanism of HER2 Rapid Internalization and …
A bispecific tetravalent anti-HER2 antibody (anti-HER2-Bs), targeting two non-overlapping epitopes on HER2 in domain IV (trastuzumab) and domain II (39S), has been reported to induce rapid internalization and efficient degradation of HER2 receptors.
An anti-HER2 biparatopic antibody that induces unique HER2
2023年3月13日 · Here, we engineer an anti-HER2 IgG1 bispecific, biparatopic antibody (Ab), zanidatamab, with unique and enhanced functionalities compared to both trastuzumab and the combination of...
Internalization and Recycling of the HER2 Receptor on Human …
However, Trastuzumab induces HER2 internalization and intracellular degradation when combined with Pertuzumab (Perjeta), another noncompetitive anti-HER2 antibody, or L26 antibody that, similar to Pertuzumab, inhibits HER2 heterodimerization with the other members of the EGFR family [24-26].
Mathematical modeling of drug-induced receptor internalization in the ...
2019年9月3日 · Trastuzumab, an approved drug to treat this type of breast cancer, is a monoclonal antibody directly binding at the HER2 receptor and ultimately inhibiting cancer cell growth. The goal of our...
HER2 Dimerization Inhibitor Pertuzumab – Mode of Action and …
There is preclinical evidence for the synergy of trastuzumab and pertuzumab in HER2-overexpressing tumors and specifically in HER2-overexpressing breast cancer. It was demonstrated that trastuzumab and pertuzumab synergistically inhibited the survival of HER2-overexpressing BT474 breast cancer cells in vitro .
Engineering a HER2-specific antibody–drug conjugate to increase ...
2019年4月1日 · We improve the potency of antibody–drug conjugates (ADCs) containing the human epidermal growth factor receptor 2 (HER2)-specific antibody pertuzumab by substantially reducing their affinity...
A novel HER2-targeting antibody 5G9 identified by large-scale ...
2020年10月1日 · Compared to pertuzumab, 5G9 demonstrated more potent synergistic cell growth inhibitory activity when combined with trastuzumab (85% vs. 55%, P<0.001). In addition, 5G9 exhibited a higher internalization rate than pertuzumab (20% vs. 9%, P<0.05), and was able to further synergize with trastuzumab to promote antigen-antibody endocytosis.
Toward Understanding the Binding Synergy of Trastuzumab and Pertuzumab ...
The radiolabeled immunoconjugates served as an important tool for experimental characterization of interaction between pertuzumab and trastuzumab to HER2. Studies with fluorescent antibodies corroborated the binding data and provided evidence of colocalization and internalization of both the antibodies in HER2-positive cells.
The Internalization and Therapeutic Activity of Antibody Drug ...
2023年4月19日 · Benefit from high internalization efficiency of MEDI4276 and the hindrance of HER2-HER3 dimerization by binding epitope of 39S, MEDI4276 could kill T-DM1-resistant HER2 low expression tumor cells, which could expand the application scope of …
HER2-Mediated Internalization of Cytotoxic Agents in
2020年5月1日 · Here we demonstrate that HER2 ubiquitination and internalization, rather than its overexpression, are key mechanisms underlying endocytosis and consequent efficacy of the anti-HER2 antibody–drug conjugates (ADC) ado-trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) in lung cancer cell lines and patient-derived xenograft models.