ArticleBreast cancer research and treatment2022
Trastuzumab does not bind rat or mouse ErbB2/neu: implications for selection of non-clinical safety models for trastuzumab-based therapeutics.
Article in Breast cancer research and treatment, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 30 citations in OpenAlex.
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- Modulation of HER2 internalization enhances single-dose antibody-drug potency in HER2Scientific reports · 2025Article
- Whole-Body Physiologically Based Pharmacokinetic Modeling Framework for Tissue Target Engagement of CD3 Bispecific Antibodies.Pharmaceutics · 2025Article
- Measurement of specific and nonspecific tissue uptake of antibodies in tumor by SPECT imaging and nonlinear compartmental modeling.EJNMMI research · 2025Article
- An IgE antibody targeting HER2 identified by clonal selection restricts breast cancer growth via immune-stimulating activities.Journal of experimental & clinical cancer research : CR · 2025Article
- Preclinical Comparison of [Molecular pharmaceutics · 2025Article
- HER2 expression in different cell lines at different inoculation sites assessed by [Pathology oncology research : POR · 2025Article
- Development of cellular models expressing cynomolgus (Frontiers in pharmacology · 2025Article
- Towards a platform quantitative systems pharmacology (QSP) model for preclinical to clinical translation of antibody drug conjugates (ADCs).Journal of pharmacokinetics and pharmacodynamics · 2024Article
- The HER2-directed antibody-drug conjugate DHES0815A in advanced and/or metastatic breast cancer: preclinical characterization and phase 1 trial results.Nature communications · 2024Article
- Priorities in Cardio-Oncology Basic and Translational Science: GCOS 2023 Symposium Proceedings:JACC. CardioOncology · 2023Review
- No Interference of H9 Extract on Trastuzumab Pharmacokinetics in Their Combinations.International journal of molecular sciences · 2023Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeAssessment of non-clinical safety signals relies on understanding species selectivity of antibodies. This is particularly important with antibody-drug conjugates, where it is key to determine target-dependent versus target-independent toxicity. Although it appears to be widely accepted that trastuzumab does not bind mouse or rat HER2/ErbB2/neu, numerous investigators continue to use mouse models to investigate safety signals of trastuzumab and trastuzumab emtansine (T-DM1). We, therefore, conducted a broad array of both binding and biologic studies to demonstrate selectivity of trastuzumab for human HER2 versus mouse/rat neu.
methodsBinding of anti-neu and anti-HER2 antibodies was assessed by ELISA, FACS, IHC, Scatchard, and immunoblot methods in human, rat, and mouse cell lines. In human hepatocytes, T-DM1 uptake and catabolism were measured by LC-MS/MS; cell viability changes were determined using CellTiter-Glo.
resultsOur data demonstrate, using different binding methods, lack of trastuzumab binding to rat or mouse neu. Structural studies show important amino acid differences in the trastuzumab-HER2 binding interface between mouse/rat and human HER2 ECD. Substitution of these rodent amino acid residues into human HER2 abolish binding of trastuzumab. Cell viability changes, uptake, and catabolism of T-DM1 versus a DM1 non-targeted control ADC were comparable, indicating target-independent effects of the DM1-containing ADCs. Moreover, trastuzumab binding to human or mouse hepatocytes was not detected.
conclusionsThese data, in total, demonstrate that trastuzumab, and by extension T-DM1, do not bind rat or mouse neu, underscoring the importance of species selection for safety studies investigating trastuzumab or trastuzumab-based therapeutics.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.