ArticleScientific reports2016
A humanized anti-DLL4 antibody promotes dysfunctional angiogenesis and inhibits breast tumor growth.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Signaling pathway dysregulation in breast cancer.Oncotarget · 2025Review
- Effects and mechanisms of exosomes in microenvironment angiogenesis in breast cancer: An updated review.Oncology research · 2025Review
- Oncogenic signaling-mediated regulation of chromatin during tumorigenesis.Cancer metastasis reviews · 2023Review
- Mammary Development and Breast Cancer: a Notch Perspective.Journal of mammary gland biology and neoplasia · 2021Review
- DR-5 and DLL-4 mAb Functionalized SLNs of Gamma-Secretase Inhibitors- An Approach for TNBC Treatment.Advanced pharmaceutical bulletin · 2021Review
- Targeting Notch in oncology: the path forward.Nature reviews. Drug discovery · 2021Review
- Review
- The complexity of tumour angiogenesis based on recently described molecules.Contemporary oncology (Poznan, Poland) · 2021Review
- Therapeutic Targeting of Notch Signaling: From Cancer to Inflammatory Disorders.Frontiers in cell and developmental biology · 2021Review
- The many facets of Notch signaling in breast cancer: toward overcoming therapeutic resistance.Genes & development · 2020Review
- Review
- The Role of DLLs in Cancer: A Novel Therapeutic Target.OncoTargets and therapy · 2020Review
- Two engineered site-specific antibody-drug conjugates, HLmD4 and HLvM4, have potent therapeutic activity in two DLL4-positive tumour xenograft models.American journal of cancer research · 2020Article
- Heritable modifiers of the tumor microenvironment influence nanoparticle uptake, distribution and response to photothermal therapy.Theranostics · 2020Article
- Frequent Activation of Notch Signaling Pathway in Colorectal Cancers and Its Implication in Patient Survival Outcome.Journal of oncology · 2020Article
- Antibody Structure and Function: The Basis for Engineering Therapeutics.Antibodies (Basel, Switzerland) · 2019Review
- Humanization of Antibodies using a Statistical Inference Approach.Scientific reports · 2018Article
- Notch signaling triggered via the ligand DLL4 impedes M2 macrophage differentiation and promotes their apoptosis.Cell communication and signaling : CCS · 2018Article
- New Perspectives on Diagnosis and Therapy of Malignant Pleural Mesothelioma.Frontiers in oncology · 2018Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Blockage of Delta-like 4 (DLL4)-directed Notch signaling induces excessive tip cell formation and endothelial proliferation resulting in dysfunctional angiogenesis in tumors. MMGZ01, as a murine anti-human DLL4 monoclonal antibody, specifically binds to human DLL4 and blocks Notch pathway. Here, the structure of MMGZ01 variable fragment (Fv) was established and framework region (FR) residues which supported complementarily determining region (CDR) loop conformation were identified. Important residues interactions were also identified through docking MMGZ01 Fv with antigen epitope in DLL4. To humanize the murine antibody, we modified MMGZ01 Fv through CDR grafting and the reconstructed antibody (H3L2) maintained similar structure and binding affinity to parental MMGZ01 after back mutation of 12 canonical murine residues in the FRs. Meanwhile, H3L2 promoted human umbilical vein endothelial cell (HUVEC) proliferation through inhibiting DLL4-directed Notch pathway. Moreover, in MDA-MB-231-bearing nude mice, H3L2 induced dysfunctional angiogenesis and tumor cell apoptosis and showed superior anti-tumor activity. In conclusion, H3L2 is an ideal humanized antibody that inhibits tumor growth through targeting DLL4-Notch pathway and has attracting potentials for clinical applications.
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Registered trials
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.