ArticleMolecular cancer therapeutics2016
Reduced Shedding of Surface Mesothelin Improves Efficacy of Mesothelin-Targeting Recombinant Immunotoxins.
Article in Molecular cancer therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 34 citations in OpenAlex.
- JNJ-79032421, a Novel Membrane-Restricted Mesothelin-Targeting T Cell-Engaging Bispecific Antibody for the Treatment of Mesothelin-Positive Cancers.Molecular cancer therapeutics · 2026Article
- Review
- Rapid CAR screening and circRNA-driven CAR-NK cells for persistent shed-resistant immunotherapy.Signal transduction and targeted therapy · 2026Article
- Ibrutinib and PD-1 Blockade Potentiate Mesothelin-Targeting CAR T-cell Therapy in Preclinical Models of Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Fc-Engineering Improves PET Imaging of Anti-Mesothelin VH-Fc across Multiple Tumor Mouse Models and Reveals Sex-Specific Renal Clearance.Bioconjugate chemistry · 2026Article
- Evaluating mesothelin as an immunotherapeutic target for endogenous T cells.Frontiers in immunology · 2026Article
- RO4, a high-affinity humanized antibody against the juxtamembrane region of mesothelin for targeted cancer therapy.Antibody therapeutics · 2026Article
- CD33Journal for immunotherapy of cancer · 2025Article
- Evaluating therapeutic plasma exchange and protease inhibitors as mechanisms to reduce soluble mesothelin.Scientific reports · 2025Article
- A humanized anti-MSLN×4-1BB bispecific antibody exhibits potent antitumour activity through 4-1BB signaling activation and fc function without systemic toxicity.Journal of translational medicine · 2025Article
- CYpHER: Catalytic extracellular targeted protein degradation with high potency and durable effect.bioRxiv : the preprint server for biology · 2024Article
- An engineered T-cell engager with selectivity for high mesothelin-expressing cells and activity in the presence of soluble mesothelin.Oncoimmunology · 2023Article
- Transient Inhibition of Trastuzumab-Tumor Binding to Overcome the "Binding-Site Barrier" and Improve the Efficacy of a Trastuzumab-Gelonin Immunotoxin.Molecular cancer therapeutics · 2022Article
- Strategies to mitigate the on- and off-target toxicities of recombinant immunotoxins: an antibody engineering perspective.Antibody therapeutics · 2022Review
- Low serum mesothelin in pancreatic cancer patients results from retention of shed mesothelin in the tumor microenvironment.Translational oncology · 2022Article
- Highly active CAR T cells that bind to a juxtamembrane region of mesothelin and are not blocked by shed mesothelin.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Development and Evaluation of Competitive Inhibitors of Trastuzumab-HER2 Binding to Bypass the Binding-Site Barrier.Frontiers in pharmacology · 2022Article
- Therapeutic Targeting of Mesothelin with Chimeric Antigen Receptor T Cells in Acute Myeloid Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Strategies to enhance monoclonal antibody uptake and distribution in solid tumors.Cancer biology & medicine · 2021Review
- Transient Competitive Inhibition Bypasses the Binding Site Barrier to Improve Tumor Penetration of Trastuzumab and Enhance T-DM1 Efficacy.Cancer research · 2021Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Mesothelin (MSLN) is a differentiation antigen that is highly expressed in many epithelial cancers. MSLN is an important therapeutic target due to its high expression in cancers and limited expression in normal human tissues. Although it has been assumed that shed antigen is a barrier to immunotoxin action, a modeling study predicted that shed MSLN may enhance the action of MSLN-targeting recombinant immunotoxins such as SS1P and similar therapeutics by facilitating their redistribution within tumors. We aimed to determine whether shed MSLN enhances or reduces the antitumor effect of MSLN-targeting immunotoxins SS1P and RG7787. We engineered a cell line, A431/G9 (TACE mutant) that expresses a mutant form of MSLN in which the TNF-converting enzyme protease site is replaced with GGGS. We compared the response of the TACE-mutant cells with immunotoxins SS1P and RG7787 with that of the parental A431/H9 cell line. We show that TACE-mutant cells shed 80% less MSLN than A431/H9 cells, that TACE-mutant cells show a 2- to 3-fold increase in MSLN-targeted immunotoxin uptake, and that they are about 5-fold more sensitive to SS1P killing in cell culture. Tumors with reduced shedding respond significantly better to treatment with SS1P and RG7787. Our data show that MSLN shedding is an impediment to the antitumor activity of SS1P and RG7787. Approaches that decrease MSLN shedding could enhance the efficacy of immunotoxins and immunoconjugates targeting MSLN-expressing tumors. Mol Cancer Ther; 15(7); 1648-55. ©2016 AACR.
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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 OpenQuestion graph.