ArticleJournal of translational medicine2013
Trastuzumab mediates antibody-dependent cell-mediated cytotoxicity and phagocytosis to the same extent in both adjuvant and metastatic HER2/neu breast cancer patients.
Article in Journal of translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 1 of them a synthesis that pooled it.
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Who cites it
116 citing papers in PubMed, 1 synthesis or guideline pooled it, 183 citations in OpenAlex.
- Dawn of Monitoring Regulatory T Cells in (Pre-)clinical Studies: Their Relevance Is Slowly Recognised.Frontiers in medicine · 2020Pooled it
- Determinants of Response to Sequential Pembrolizumab with Trastuzumab plus Platinum/5-FU in HER2-Positive Gastric Cancer: A Phase II Chemoimmunotherapy Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- A Phase 1 randomized study compare the pharmacokinetics, safety and immunogenicity of HLX02 to reference CN- and EU-sourced trastuzumab in healthy subjects.Cancer chemotherapy and pharmacology · 2021Trial
- Personalized medicine, scientific revolution or self-serving illusion: viewpoint from EORTC-PAMM Group.ESMO open · 2026Review
- Bispecific antibody AP402 targets p95HER2 and induces costimulation through CD137 to improve efficacy for HER2-positive tumors.Molecular medicine (Cambridge, Mass.) · 2026Article
- A novel therapeutic monoclonal antibody targeting PZR demonstrates potent anti-metastatic efficacy in triple-negative breast cancer.Journal of translational medicine · 2026Article
- Development of a STEAP1-Targeted Prostate Cancer Specific Antibody Drug Conjugate Platform with Immunostimulatory Properties.Research square · 2026Article
- Review
- Review
- Comparison of the efficacy and safety of HLX-02 plus pertuzumab versus HLX-02 plus pyrotinib in neoadjuvant therapy for HER2-positive breast cancer.Therapeutic advances in medical oncology · 2026Article
- Long Non-Coding RNAs in HER2-Positive Breast Cancer: From Resistance Mechanisms to Translational Potential.Oncology research · 2026Review
- Review
- Surface plasmon resonance microscopy reveals N-glycosylation driven modulation of affinity and avidity of ErbB receptors in whole single pancreatic cancer cells.Glycobiology · 2025Article
- Target cell adhesion limits macrophage phagocytosis and promotes trogocytosis.The Journal of cell biology · 2025Article
- Analyses of Exosomal HER2 in Breast Cancer and the Effect of Respective Exosome-Immune Complexes on Trastuzumab-Based Immunotherapy.International journal of molecular sciences · 2025Article
- Mitigating Trastuzumab-Doxorubicin Cardiotoxicity With Multiscale Quantitative Systems Toxicology and PBPK-Toxicodynamic Predictive Modeling Framework.CPT: pharmacometrics & systems pharmacology · 2025Article
- Review
- Effect of delayed isolation of peripheral blood mononuclear cells on cell viability and functionality.BMC immunology · 2025Article
- NK cell immunopotentiators-loaded nanoliposomes enhance ADCC effect for targeted therapy against HER2-positive breast cancer.Cell communication and signaling : CCS · 2025Article
- Target cell adhesion limits macrophage phagocytosis and promotes trogocytosis.bioRxiv : the preprint server for biology · 2025Article
56 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMonoclonal antibodies (mAb), such as trastuzumab are a valuable addition to breast cancer therapy. Data obtained from neoadjuvant settings revealed that antibody-dependent cell-mediated cytotoxicity (ADCC) is a major mechanism of action for the mAb trastuzumab. Conflicting results still call into question whether disease progression, prolonged treatment or concomitant chemotherapy influences ADCC and related immunological phenomena.
methodsWe analyzed the activity of ADCC and antibody-dependent cell-mediated phagocytosis (ADCP) of peripheral blood mononuclear cells (PBMCs) from human epidermal growth factor receptor 2 (HER2/neu) positive breast cancer patients receiving trastuzumab therapy either in an adjuvant (n = 13) or metastatic (n = 15) setting as well as from trastuzumab treatment-naive (t-naive) HER2/neu negative patients (n = 15). PBMCs from healthy volunteers (n = 24) were used as controls. ADCC and ADCP activity was correlated with the expression of antibody binding Fc-gamma receptor (FcγR)I (CD64), FcγRII (CD32) and FcγRIII (CD16) on CD14+ (monocytes) and CD56+ (NK) cells, as well as the expression of CD107a+ (LAMP-1) on CD56+ cells and the total amount of CD4+CD25+FOXP3+ (Treg) cells. In metastatic patients, markers were correlated with progression-free survival (PFS).
resultsADCC activity was significantly down regulated in metastatic, adjuvant and t-naive patient cohorts as compared to healthy controls. Reduced ADCC activity was inversely correlated with the expression of CD107a on CD56+ cells in adjuvant patients. ADCC and ADCP activity of the patient cohorts were similar, regardless of treatment duration or additional chemotherapy. PFS in metastatic patients inversely correlated with the number of peripheral Treg cells.
conclusionThe reduction of ADCC in patients as compared to healthy controls calls for adjuvant strategies, such as immune-enhancing agents, to improve the activity of trastuzumab. However, efficacy of trastuzumab-specific ADCC and ADCP appears not to be affected by treatment duration, disease progression or concomitant chemotherapy. This finding supports the application of trastuzumab at any stage of the disease.
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