ArticleNPJ precision oncology2023
Chimeric antibody targeting unique epitope on onco-mucin16 reduces tumor burden in pancreatic and lung malignancies.
Article in NPJ precision oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 30 citations in OpenAlex.
- Targeting cancer-associated fibroblast-driven LIF/LIFR axis improves the therapeutic efficacy of gemcitabine and nab-paclitaxel in pancreatic cancer.NPJ precision oncology · 2025Article
- Emerging pathways yielding opportunities for future treatments in pancreatic ductal adenocarcinoma.Expert opinion on therapeutic targets · 2025Review
- Muc16CD is a novel CAR T cell target antigen for the treatment of pancreatic cancer.Molecular therapy. Oncology · 2024Article
- Non-small cell lung cancer organoids: Advances and challenges in current applications.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Secretory Trefoil Factor 1 (TFF1) promotes gemcitabine resistance through chemokine receptor CXCR4 in Pancreatic Ductal Adenocarcinoma.Cancer letters · 2024Article
- MUC16: clinical targets with great potential.Clinical and experimental medicine · 2024Review
- Mesothelin-based CAR-T cells exhibit potent antitumor activity against ovarian cancer.Journal of translational medicine · 2024Article
- Virus-like particle vaccine displaying an external, membrane adjacent MUC16 epitope elicits ovarian cancer-reactive antibodies.Journal of ovarian research · 2024Article
- Targeted radiopharmaceuticals: an underexplored strategy for ovarian cancer.Theranostics · 2024Review
- MUC1 and MUC16: critical for immune modulation in cancer therapeutics.Frontiers in immunology · 2024Review
- Mucins 3A and 3B Are Expressed in the Epithelium of Human Large Airway.International journal of molecular sciences · 2023Observational
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Authors and funding
22 authors at 4 institutions in 1 country.
Funding
Abstract
Aberrantly expressed onco-mucin 16 (MUC16) and its post-cleavage generated surface tethered carboxy-terminal (MUC16-Cter) domain are strongly associated with poor prognosis and lethality of pancreatic (PC) and non-small cell lung cancer (NSCLC). To date, most anti-MUC16 antibodies are directed towards the extracellular domain of MUC16 (CA125), which is usually cleaved and shed in the circulation hence obscuring antibody accessibility to the cancer cells. Herein, we establish the utility of targeting a post-cleavage generated, surface-tethered oncogenic MUC16 carboxy-terminal (MUC16-Cter) domain by using a novel chimeric antibody in human IgG1 format, ch5E6, whose epitope expression directly correlates with disease severity in both cancers. ch5E6 binds and interferes with MUC16-associated oncogenesis, suppresses the downstream signaling pFAK(Y397)/p-p70S6K(T389)/N-cadherin axis and exert antiproliferative effects in cancer cells, 3D organoids, and tumor xenografts of both PC and NSCLC. The robust clinical correlations observed between MUC16 and N-cadherin in patient tumors and metastatic samples imply ch5E6 potential in targeting a complex and significantly occurring phenomenon of epithelial to mesenchymal transition (EMT) associated with disease aggressiveness. Our study supports evaluating ch5E6 with standard-of-care drugs, to potentially augment treatment outcomes in malignancies inflicted with MUC16-associated poor prognosis.
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Registered trials
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