ArticleMolecular oncology2013
Lipoplex mediated silencing of membrane regulators (CD46, CD55 and CD59) enhances complement-dependent anti-tumor activity of trastuzumab and pertuzumab.
Article in Molecular oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 108 citations in OpenAlex.
- HER2 targeted therapy resistance in breast cancer: from molecular landscape to clinical aspects.Science China. Life sciences · 2026Review
- Humoral immunity in cancer.Signal transduction and targeted therapy · 2026Review
- Cancer-Specific Antihuman Podoplanin Antibody chLpMab-2f Exerts Antitumor Effects Against Pleural Mesothelioma.Cancer science · 2026Article
- Complement system in cancer: friend or foe of immunotherapy.Journal for immunotherapy of cancer · 2026Review
- Shaping Tumor Microenvironment by Amplifying the Complement Cascade for Improved Immune Response in Pancreatic Cancer Model.Molecular cancer therapeutics · 2026Article
- The role of the complement system in gastrointestinal-related diseases.Frontiers in immunology · 2026Review
- The application of antibody-based agents in cancer therapy based on their mechanisms of action.Fundamental research · 2025Review
- Fighting HER2 in Gastric Cancer: Current Approaches and Future Landscapes.International journal of molecular sciences · 2025Review
- Chemotherapy of breast cancer cells alters susceptibility to complement-mediated opsonization and killing.Medical oncology (Northwood, London, England) · 2025Article
- Antitumor Activities of a Humanized Cancer-Specific Anti-HER2 Monoclonal Antibody, humHInternational journal of molecular sciences · 2025Article
- Directed-Complement Activation as a Novel Immunotherapeutic Approach for HER2-Breast Cancer.ImmunoTargets and therapy · 2025Article
- CD46 TREM1 regulates the autophagy marker LC3B ATG5 in oral squamous cell carcinoma.Frontiers in oncology · 2025Article
- PK/PD Evaluation of Antibody-Drug Conjugates with Enhanced Immune Effector Functions.The AAPS journal · 2024Article
- Identifying a CD8T cell signature in the tumor microenvironment to forecast gastric cancer outcomes from sequencing data.Journal of gastrointestinal oncology · 2024Article
- Anti-HER2 Cancer-Specific mAb, HInternational journal of molecular sciences · 2024Article
- New Frontiers in the Treatment of Patients with HER2+ Cancer and Brain Metastases: Is Radiotherapy Always Useful?Cancers · 2024Review
- Lipoplexes' Structure, Preparation, and Role in Managing Different Diseases.AAPS PharmSciTech · 2024Review
- Informed by Cancer Stem Cells of Solid Tumors: Advances in Treatments Targeting Tumor-Promoting Factors and Pathways.International journal of molecular sciences · 2024Review
- Molecular Targeting of the Human Epidermal Growth Factor Receptor-2 (HER2) Genes across Various Cancers.International journal of molecular sciences · 2024Review
- Unlocking the Power of Complement-Dependent Cytotoxicity: Engineering Strategies for the Development of Potent Therapeutic Antibodies for Cancer Treatments.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
12 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The therapeutic potential of anticancer antibodies is limited by the resistance of tumor cells to complement-mediated attack, primarily through the over-expression of membrane complement regulatory proteins (mCRPs: CD46, CD55 and CD59). Trastuzumab, an anti- HER2 monoclonal antibody, approved for the treatment of HER2-positive breast and gastric cancers, exerts only minor complement-mediated cytotoxicity (CDC). Pertuzumab is a novel anti-HER2 monoclonal antibody, which blocks HER2 dimerization with other ligand-activated HER family members. Here, we explored the complement-mediated anti-tumor effects of trastuzumab and pertuzumab on HER2-positive tumor cells of various histological origins. Delivery of chemically stabilized anti-mCRP siRNAs using cationic lipoplexes, AtuPLEXes, to HER2-over-expressing BT474, SK-BR-3 (breast), SKOV3 (ovarian) and Calu-3 (lung) cancer cells reduced mCRPs expression by 85-95%. Knockdown of individual complement regulators variably led to increased CDC only upon combined treatment with trastuzumab and pertuzumab. The combined down-regulation of all the three regulators augmented CDC by 48% in BT474, 46% in SK-BR-3 cells, 78% in SKOV3 cells and by 30% in Calu-3 cells and also increased complement-induced apoptosis and caspase activity on mCRP neutralized tumor cells. In addition, antibody-induced C3 opsonization of tumor cells was significantly enhanced after mCRP silencing and further augmented tumor cell killing by macrophages. Our findings suggest that siRNA-induced inhibition of complement regulator expression clearly enhances complement- and macrophage-mediated anti-tumor activity of trastuzumab and pertuzumab on HER2-positive tumor cells. Thus - if selectively targeted to the tumor - siRNA-induced inhibition of complement regulation may serve as an innovative strategy to potentiate the efficacy of antibody-based immunotherapy.
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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.