ArticleJournal of translational medicine2024
Dual targeting non-overlapping epitopes in HER2 domain IV substantially enhanced HER2/HER2 homodimers and HER2/EGFR heterodimers internalization leading to potent antitumor activity in HER2-positive human gastric cancer.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- [Novel therapeutic strategies for liver metastases driven by the common microenvironment].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Albumin binding improves the pharmacokinetics and therapeutic efficacy of aScience advances · 2026Article
- Antibody-Drug Conjugates Targeting Resistance-Associated Signaling Pathways: Recent Advances and Future Perspectives.International journal of molecular sciences · 2026Review
- Antibody-drug conjugates in cancer therapy: current landscape, challenges, and future directions.Molecular cancer · 2025Review
- Evolving Landscape of HER2-Targeted Therapies for Gastric Cancer Patients.Current treatment options in oncology · 2025Review
- Human Epidermal Growth Factor Receptor 2 Positive Advanced Gastric or Esophagogastric Adenocarcinoma: Reflecting on the Past to Gain a New Insights.Current oncology reports · 2025Review
- The influence ofFrontiers in immunology · 2025Article
- Article
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Abstract
backgroundTrastuzumab and pertuzumab combination has been approved for the treatment of patients with HER2-positive metastatic breast cancer. However, trastuzumab and pertuzumab combination did not show improvement in overall survival in patients with HER2-positive metastatic gastric cancer.
methodsWe developed a new HER2-targeted monoclonal antibody, HLX22, targeting HER2 subdomain IV as trastuzumab but with non-overlapping epitopes. We examined the antitumor effects of this novel HER2-antibody in gastric cell lines and cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models.
resultsHLX22 in combination with HLX02 (trastuzumab biosimilar) induced enhancement of HER2/HER2 homodimers and HER2/EGFR heterodimers internalization, which ultimately led to the reduction in signal transductions involving STAT3, P70 S6, and AKT; gene expressions of FGF-FGFR-PI3K-MTOR, EGF-EGFR-RAS, TGF-β-SMAD, PLCG and cell cycle progression related pathways that favor tumor development, proliferation, progression, migration and survival in gastric cancer cell line NCI-N87 were also reduced. These differing but complementary actions contributed to the synergistic antitumor efficacy of the HLX22 and HLX02 combination in gastric cancer cell lines, CDX and PDX. In addition, HLX22 in combination with HLX02 demonstrated stronger antitumor efficacy than HLX02 and HLX11 (a potential pertuzumab biosimilar) combination treatment both in vitro and in vivo.
conclusionsThese results suggested that the application of non-competing antibodies HLX22 and HLX02 targeting HER2 subdomain IV together may be of substantial benefit to gastric cancer patients who currently respond suboptimal to trastuzumab therapy.
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