ArticleScientific reports2020
A novel anti-HER2 antibody GB235 reverses Trastuzumab resistance in HER2-expressing tumor cells in vitro and in vivo.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 24 citations in OpenAlex.
- Article
- Development of Novel Neratinib and Docetaxel Core-Loaded and Trastuzumab Surface-Conjugated Nanoparticle for Treatment of HER-2 Positive Breast Cancer.Pharmaceutics · 2025Article
- Nanotechnology Platform for the Delivery of Docetaxel and Tyrosine Kinase Inhibitors for HER2-Positive Breast Cancer Therapy.Pharmaceutical nanotechnology · 2025Article
- Biparatopic HER2-targeted nanobody binder synergizes with trastuzumab in resistant tumor cells.Frontiers in immunology · 2025Article
- T cells expressing a HER2-specific chimeric antigen receptor as treatment for breast cancer.Journal of cancer research and clinical oncology · 2023Article
- Review
- HSD17B4 methylation enhances glucose dependence of BT-474 breast cancer cells and increases lapatinib sensitivity.Breast cancer research and treatment · 2023Article
- Targeting Tn-positive tumors with an afucosylated recombinant anti-Tn IgG.Scientific reports · 2023Article
- A novel nanobody-based HER2-targeting antibody exhibits potent synergistic antitumor efficacy in trastuzumab-resistant cancer cells.Frontiers in immunology · 2023Article
- Prevention and Therapy of Metastatic HER-2Biomedicines · 2022Article
- Review
- Nanotechnology in the development of small and large molecule tyrosine kinase inhibitors and immunotherapy for the treatment of HER2-positive breast cancer.Journal of cancer & metastasis research · 2022Article
- Fully human recombinant antibodies against EphA2 from a multi-tumor patient immune library suitable for tumor-targeted therapy.Bioengineered · 2021Article
- Potent synergistic anti-tumor activity of a novel humanized anti-HER2 antibody hersintuzumab in combination with trastuzumab in xenograft models.Investigational new drugs · 2021Article
- Photodynamic Therapy for the Treatment and Diagnosis ofFrontiers in chemistry · 2021Review
- Case Report: Herceptin as a Potentially Valuable Adjuvant Therapy for a Patient With Human Epidermal Growth Factor Receptor 2-Positive Advanced Esophageal Squamous Cell Carcinoma.Frontiers in oncology · 2020Article
- A Novel Anti-HER2 Bispecific Antibody With Potent Tumor Inhibitory EffectsFrontiers in immunology · 2020Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HER2 overexpression is frequently associated with tumor metastasis and poor prognosis of breast cancer. More evidence indicates that HER3 is involved in HER2-resistant therapies. Combination treatments with two or more different monoclonal antibodies are a promising strategy to overcome resistance to HER2 therapies. We presented a novel fully human HER2-targeted monoclonal antibody, GB235, screened from a phage-display library against the HER2 antigen. GB235 in combination with Trastuzumab overcomes resistance in HER2-positive tumors and results in more sustained inhibition of tumor growth over time. The competition binding assay showed that the epitopes of GB235 do not overlap with those of Pertuzumab and Trastuzumab on HER2. Further HER2 mutagenesis results revealed that the binding epitopes of GB235 were located in the domain III of HER2. The mechanism of action of GB235 in blocking HER2-driven tumors is different from the mechanisms of Trastuzumab or Pertuzumab. GB235 does not affect the heterodimerization of HER2 and HER3, whereas the GB235 combined treatment with Trastuzumab significantly inhibited heregulin-induced HER3 phosphorylation and downstream signaling. Moreover, GB235 in combination with Trastuzumab reversed the resistance to heregulin-induced proliferation in HER2-overexpressing cancer cell lines. GB235 combined with Trastuzumab treatment in xenograft models resulted in improved antitumor activity. Complete tumor suppression was observed in the HER2-positive NCI-N87 xenograft model treated with the combination treatment with GB235 and Trastuzumab. In a Trastuzumab-resistant patient-derived tumor xenograft model GA0060, GB235 plus Trastuzumab reversed the resistance to Trastuzumab monotherapy. Because GB235 showed a different working mechanism with Pertuzumab and Trastuzumab, these agents can be considered complementary therapy against HER2 overexpression tumors.
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