ArticleOncotarget2017
Mesothelin-targeted immunotoxin RG7787 has synergistic anti-tumor activity when combined with taxanes.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
21 citing papers in PubMed, 26 citations in OpenAlex.
- Phase I/II Study of the Mesothelin-targeted Immunotoxin LMB-100 with Nab-Paclitaxel for Patients with Advanced Pancreatic Adenocarcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- RO4, a high-affinity humanized antibody against the juxtamembrane region of mesothelin for targeted cancer therapy.Antibody therapeutics · 2026Article
- Targeting Mesothelin in Solid Tumours: Anti-mesothelin Antibody and Drug Conjugates.Current oncology reports · 2023Review
- Systemic immune changes accompany combination treatment with immunotoxin LMB-100 and nab-paclitaxel.Cancer medicine · 2023Article
- Antibody-Based Approaches to Target Pancreatic Tumours.Antibodies (Basel, Switzerland) · 2022Review
- Review
- Review
- Phase 1 study of the immunotoxin LMB-100 in patients with mesothelioma and other solid tumors expressing mesothelin.Cancer · 2020Article
- Anti-BCMA Immunotoxins: Design, Production, and Preclinical Evaluation.Biomolecules · 2020Review
- Mesothelin-Targeted Recombinant Immunotoxins for Solid Tumors.Biomolecules · 2020Review
- From Malignant Progression to Therapeutic Targeting: Current Insights of Mesothelin in Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2020Review
- Mesothelin Enhances Tumor Vascularity in Newly Forming Pancreatic Peritoneal Metastases.Molecular cancer research : MCR · 2020Article
- Acquired Resistance to Antibody-Drug Conjugates.Cancers · 2019Review
- Mesothelin as a biomarker for targeted therapy.Biomarker research · 2019Review
- Article
- The Role of Mesothelin as a Diagnostic and Therapeutic Target in Pancreatic Ductal Adenocarcinoma: A Comprehensive Review.Targeted oncology · 2018Review
- Chimeric antigen receptor T cell therapy in pancreatic cancer: from research to practice.Medical oncology (Northwood, London, England) · 2018Review
- Panbinostat decreases cFLIP and enhances killing of cancer cells by immunotoxin LMB-100 by stimulating the extrinsic apoptotic pathway.Oncotarget · 2017Article
- Article
- Paclitaxel synergizes with exposure time adjusted CD22-targeting immunotoxins against B-cell malignancies.Oncotarget · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Recombinant immunotoxins (RITs) are antibody-based therapeutics that carry a toxin payload. The RG7787 RIT targets the cancer antigen mesothelin to deliver a recombinantly-engineered, reduced immunogenicity variant of Pseudomonas exotoxin A (PE) to the cytosol where it inhibits protein synthesis. Here we demonstrate that maximal doses of RG7787 temporarily halt growth of pancreatic cancer tumor xenografts, similar to the approved drugs gemcitabine and nab-paclitaxel, however, combination of the RIT with nab-paclitaxel produces durable complete regressions in most mice. Synergy between taxane and anti-MSLN RITs has been previously demonstrated in mouse models, but direct interaction of the combination in cell culture was not observed. Here, we show that this favorable interaction occurs in cell culture, is dependent on the dose and duration of RG7787 exposure, requires the catalytically active PE, and still occurs with RIT targeting a non-MSLN surface antigen. Unexpectedly, the combination does not increase RG7787-mediated protein synthesis inhibition nor perturb downstream apoptotic markers of RIT-mediated killing, but does augment levels of acetylated tubulin, a marker of taxane activity. Taken together, these data suggest that PE increases cell sensitivity to taxane-mediated killing by increasing taxane-mediated microtubule stability and priming cells for apoptosis by decreasing levels of the pro-survival factor Mcl-1.
Indexed as
Identifiers
What OpenQuestion holds
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.