ArticleScientific reports2015
A novel Monoclonal Antibody against Notch1 Targets Leukemia-associated Mutant Notch1 and Depletes Therapy Resistant Cancer Stem Cells in Solid Tumors.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- A narrative review of the distribution and role of multipotent fibroblasts in penile tissue: implications for regenerative medicine and erectile dysfunction.Translational andrology and urology · 2025Review
- Relapsed childhood T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma.Haematologica · 2025Review
- Multiscale simulations reveal architecture of NOTCH protein and ligand specific features.Biophysical journal · 2025Article
- Emerging opportunities to treat drug-resistant breast cancer: Discovery of novel small-molecule inhibitors against different targets.Frontiers in pharmacology · 2025Review
- Notch Partners in the Long Journey of T-ALL Pathogenesis.International journal of molecular sciences · 2023Review
- Notch signaling, hypoxia, and cancer.Frontiers in oncology · 2023Review
- Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives.Cancers · 2021Review
- Progress in research on childhood T-cell acute lymphocytic leukemia, Notch1 signaling pathway, and its inhibitors: A review.Bosnian journal of basic medical sciences · 2021Review
- Targeting Notch in oncology: the path forward.Nature reviews. Drug discovery · 2021Review
- Targeting oncogenic Notch signaling with SERCA inhibitors.Journal of hematology & oncology · 2021Review
- ASR490, a Small Molecule, Overrides Aberrant Expression ofMolecular cancer therapeutics · 2020Article
- Advances of target therapy on NOTCH1 signaling pathway in T-cell acute lymphoblastic leukemia.Experimental hematology & oncology · 2020Review
- Review
- Blockade of Oncogenic NOTCH1 with the SERCA Inhibitor CAD204520 in T Cell Acute Lymphoblastic Leukemia.Cell chemical biology · 2020Article
- The Genetics and Mechanisms of T-Cell Acute Lymphoblastic Leukemia.Cold Spring Harbor perspectives in medicine · 2020Review
- Therapeutic Targeting of Notch Signaling Pathway in Hematological Malignancies.Mediterranean journal of hematology and infectious diseases · 2019Review
- Colorectal cancer: genetic abnormalities, tumor progression, tumor heterogeneity, clonal evolution and tumor-initiating cells.Medical sciences (Basel, Switzerland) · 2018Review
- Article
- Notch signaling: its roles and therapeutic potential in hematological malignancies.Oncotarget · 2016Review
- Notch signaling in prostate cancer: refining a therapeutic opportunity.Histology and histopathology · 2016Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Higher Notch signaling is known to be associated with hematological and solid cancers. We developed a potential immunotherapeutic monoclonal antibody (MAb) specific for the Negative Regulatory Region of Notch1 (NRR). The MAb604.107 exhibited higher affinity for the "Gain-of-function" mutants of Notch1 NRR associated with T Acute lymphoblastic Leukemia (T-ALL). Modeling of the mutant NRR with 12 amino-acid insertion demonstrated "opening" resulting in exposure of the S2-cleavage site leading to activated Notch1 signaling. The MAb, at low concentrations (1-2 μg/ml), inhibited elevated ligand-independent Notch1 signaling of NRR mutants, augmented effect of Thapsigargin, an inhibitor of mutant Notch1, but had no effect on the wild-type Notch1. The antibody decreased proliferation of the primary T-ALL cells and depleted leukemia initiating CD34/CD44 high population. At relatively high concentrations, (10-20 μg/ml), the MAb affected Notch1 signaling in the breast and colon cancer cell lines. The Notch-high cells sorted from solid-tumor cell lines exhibited characteristics of cancer stem cells, which were inhibited by the MAb. The antibody also increased the sensitivity to Doxorubucinirubicin. Further, the MAb impeded the growth of xenografts from breast and colon cancer cells potentiated regression of the tumors along with Doxorubucin. Thus, this antibody is potential immunotherapeutic tool for different cancers.
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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 Socratic graph.