ArticleCancer research communications2023
Structures of Cancer Antigen Mesothelin and Its Complexes with Therapeutic Antibodies.
Article in Cancer research communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 26 citations in OpenAlex.
- Review
- Conformational epitope engagement by anti-MSLN ADC RC88 confers resistance to soluble mesothelin.Antibody therapeutics · 2026Article
- Review
- Mesothelin Expression in Acute Leukemia: Correlations With Immunophenotype, Cytogenetics, and Mutational Status.Applied immunohistochemistry & molecular morphology : AIMM · 2026Article
- A TRPM4-associated necrotic cell death signature for prognostic stratification in pancreatic cancer.Journal of gastrointestinal oncology · 2026Article
- T cell-inspired therapeutic delivery platforms: From nanomedicines to cell therapy.Materials today. Bio · 2026Review
- Mesothelin biology and the evolving landscape of targeted immunotherapy.Molecular therapy. Oncology · 2026Review
- A monoclonal antibody W1 blocks mesothelin-mediated tumor progression.Molecular therapy. Oncology · 2026Article
- RO4, a high-affinity humanized antibody against the juxtamembrane region of mesothelin for targeted cancer therapy.Antibody therapeutics · 2026Article
- Evaluating mesothelin as an immunotherapeutic target for endogenous T cells.Frontiers in immunology · 2026Article
- Novel perspectives on MSLN-targeted cancer therapy: from molecular mechanisms to clinical translation.Cancer biology & therapy · 2025Review
- Decoding the role of mesothelin in tumor dynamics and targeted treatment innovations.Molecular biomedicine · 2025Review
- Generating potent and persistent antitumor immunity via affinity-tuned CAR-T cells targeting mesothelin.Acta pharmacologica Sinica · 2025Article
- Computational modeling and experimental validation of the interaction between tumor biomarker mesothelin and an engineered targeting protein with therapeutic activity.Protein science : a publication of the Protein Society · 2025Article
- Enhancing theranostic potential of anti-mesothelin sdAb through site-specific labeling at a unique conserved lysine by molecular engineering.EJNMMI radiopharmacy and chemistry · 2025Article
- Advancing pancreatic cancer therapy by mesothelin-specific nanobody conjugation.Molecular cancer · 2025Article
- Review
- Potent and durable control of mesothelin-expressing tumors by a novel T cell-secreted bi-specific engager.Journal for immunotherapy of cancer · 2025Article
- Development of CAR-T Therapies and Personalized Vaccines for the Treatment of Cholangiocarcinoma: Current Progress, Mechanisms of Action, and Challenges.The American journal of pathology · 2025Review
- Excess shed mesothelin disrupts pancreatic cancer cell clustering to impair peritoneal colonization.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
The tumor-associated antigen mesothelin is expressed at high levels on the cell surface of many human cancers, while its expression in normal tissues is limited. The binding of mesothelin to the tumor-associated cancer antigen 125 (CA-125) can lead to heterotypic cell adhesion and tumor metastasis within the pleural and peritoneal cavities. Immunotherapeutic strategies targeting mesothelin are being intensively investigated. Here, we report the crystal structures of mesothelin that reveal a compact, right-handed solenoid consisting of 24 short helices and connecting loops. These helices form a nine-layered spiral coil that resembles ARM/HEAT family proteins. Glycan attachments have been identified in the structure for all three predicted N-glycosylation sites and confirmed with samples from cell culture and patient ascites. The structures of full-length mesothelin and its complex with the Fab of MORAb-009 reveal the interaction of the antibody with the complete epitope, which has not been reported previously. The N-terminal half of mesothelin is conformationally rigid, suitable for eliciting specific antibodies, whereas its C-terminal portion is more flexible. The structure of the C-terminal shedding-resistant fragment of mesothelin complexed with a mAb 15B6 displays an extended linear epitope and helps explain the protection afforded by the antibody for the shedding sites. Significance: The structures of full-length mesothelin and its complexes with antibodies reported here are the first to be determined experimentally, providing atomic models for structural organization of this protein and its interactions with antibodies. It offers insights into the function of mesothelin and guidance for further development of therapeutic antibodies.
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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.