ArticleOncotarget2016
Mesothelin's minimal MUC16 binding moiety converts TR3 into a potent cancer therapeutic via hierarchical binding events at the plasma membrane.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Turn TRAIL Into Better Anticancer Therapeutic Through TRAIL Fusion Proteins.Cancer medicine · 2025Review
- MUC16: clinical targets with great potential.Clinical and experimental medicine · 2024Review
- Harnessing ferroptosis for enhanced sarcoma treatment: mechanisms, progress and prospects.Experimental hematology & oncology · 2024Review
- Malic Enzyme 1 Absence in Synovial Sarcoma Shifts Antioxidant System Dependence and Increases Sensitivity to Ferroptosis Induction with ACXT-3102.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Glucose restriction combined with chemotherapy decreases telomere length and cancer antigen-125 secretion in ovarian carcinoma.Oncology letters · 2020Article
- Molecular Mode of Action of TRAIL Receptor Agonists-Common Principles and Their Translational Exploitation.Cancers · 2019Review
- MUC16 as a novel target for cancer therapy.Expert opinion on therapeutic targets · 2018Review
- Antibodies and Derivatives Targeting DR4 and DR5 for Cancer Therapy.Antibodies (Basel, Switzerland) · 2017Review
- Journey of TRAIL from Bench to Bedside and its Potential Role in Immuno-Oncology.Oncology reviews · 2017Review
- The Targeted SMAC Mimetic SW IV-134 is a strong enhancer of standard chemotherapy in pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2017Article
- Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
Abstract
TRAIL has been extensively explored as a cancer drug based on its tumor-selective activity profile but it is incapable per se of discriminating between death receptors expressed by normal host cells and transformed cancer cells. Furthermore, it is well documented that surface tethering substantially increases its biologic activity. We have previously reported on Meso-TR3, a constitutive TRAIL trimer targeted to the biomarker MUC16 (CA125), in which the entire ectodomain of human mesothelin was genetically fused to the TR3 platform, facilitating attachment to the cancer cells via the MUC16 receptor. Here, we designed a truncation variant, in which the minimal 64 amino acid MUC16 binding domain of mesothelin was incorporated into TR3. It turned out that the dual-domain biologic Meso64-TR3 retained its high MUC16 affinity and bound to the cancer cells quickly, independent of the TR3/death receptor interaction. Furthermore, it was substantially more potent than Meso-TR3 and TR3 in vitro and in a preclinical xenograft model of MUC16-dependent ovarian cancer. Phenotypically, Meso64-TR3 is more closely related to non-targeted TR3, evident by indistinguishable activity profiles on MUC16-deficient cancers and similar thermal stability characteristics. Overall, Meso64-TR3 represents a fully human, MUC16-targetd TRAIL-based biologic, ideally suited for exploring preclinical and clinical evaluation studies in MUC16-dependent malignancies.
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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.