ArticleEBioMedicine2020
A novel HER2-targeting antibody 5G9 identified by large-scale trastuzumab-based screening exhibits potent synergistic antitumor activity.
Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 13 citations in OpenAlex.
- Discovery and preclinical evaluation of monoclonal antibodies and bispecific engagers targeting the NKG2A inhibitory receptor.Science advances · 2026Article
- Biparatopic HER2-targeted nanobody binder synergizes with trastuzumab in resistant tumor cells.Frontiers in immunology · 2025Article
- Multiparatopic antibodies induce targeted downregulation of programmed death-ligand 1.Cell chemical biology · 2024Article
- Lapatinib-induced enhancement of mitochondrial respiration in HER2-positive SK-BR-3 cells: mechanism revealed by analysis of proteomic but not transcriptomic data.Frontiers in molecular biosciences · 2024Article
- A novel nanobody-based HER2-targeting antibody exhibits potent synergistic antitumor efficacy in trastuzumab-resistant cancer cells.Frontiers in immunology · 2023Article
- Pharmacokinetics of Monoclonal Antibody and Antibody Fragments in the Mouse Eye Following Systemic Administration.The AAPS journal · 2021Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPertuzumab is currently used in combination with trastuzumab as the first-line treatment for HER2-positive metastatic breast cancer. However, pertuzumab was originally developed independently from trastuzumab and was later incidentally found to have synergistic efficacy when combined with trastuzumab, it remains to be seen whether a more potent synergistic efficacy partner exists for trastuzumab.
methodsA trastuzumab-based functional assay was used to screen anti-HER2 antibodies harboring trastuzumab-synergistic antitumor activity. The lead candidate 5G9, in combination with trastuzumab, was further characterized for its bioactivities in cell proliferation, cell apoptosis, antigen-antibody endocytosis and HER2-mediated cell signaling pathway blocking. Finally, animal models were used to evaluate the in vivo synergistic antitumor efficacy of 5G9 in combination with trastuzumab.
findingsCompared 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. The internalization rate of the combination of 5G9 and trastuzumab was higher than that of pertuzumab and trastuzumab (35% vs. 14%, P<0.001). In vivo animal studies demonstrated that 5G9 in combination with trastuzumab showed more potent synergistic antitumor efficacy than the combination of pertuzumab and trastuzumab.
interpretation5G9, together with trastuzumab, may provide a potential opportunity for more efficacious treatment of HER2-positive cancers.
fundingNational Natural Science Foundation of China; State Key Laboratory of Analytical Chemistry for Life Science.
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