ArticlePancreas2012
A deimmunized bispecific ligand-directed toxin that shows an impressive anti-pancreatic cancer effect in a systemic nude mouse orthotopic model.
Article in Pancreas, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 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
8 citing papers in PubMed, 15 citations in OpenAlex.
- LukS-PV Inhibits Hepatocellular Carcinoma Progression by Downregulating HDAC2 Expression.Molecular therapy oncolytics · 2020Article
- LukS-PV Inhibits Hepatocellular Carcinoma Cells Migration via the TNNC1/PI3K/AKT Axis.OncoTargets and therapy · 2020Article
- Anticancer Activity of Bacterial Proteins and Peptides.Pharmaceutics · 2018Review
- Development of a Deimmunized Bispecific Immunotoxin dDT2219 against B-Cell Malignancies.Toxins · 2018Article
- Targeting of Tumor Neovasculature with GrB/VEGFBiomedicines · 2017Review
- Article
- Targeted tumor therapy by epidermal growth factor appended toxin and purified saponin: an evaluation of toxicity and therapeutic potential in syngeneic tumor bearing mice.Molecular oncology · 2013Article
- Construction and characterization of novel, completely human serine protease therapeutics targeting Her2/neu.Molecular cancer therapeutics · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveThe objective was to test a bispecific ligand-directed toxin (BLT), with reduced immunogenicity for enhanced efficacy in targeting orthotopic pancreatic cancer in vivo.
methodA new BLT was created in which both human epidermal growth factor (EGF) and interleukin 4 cytokines were cloned onto the same single chain molecule with deimmunized pseudomonas exotoxin (dEGF4KDEL). Key amino acids dictating B-cell generation of neutralizing antitoxin antibodies were mutated. Bioassays were used to determine whether mutation reduced potency, and enzyme-linked immunosorbent assay studies were performed to determine whether antitoxin antibodies were reduced. A genetically altered luciferase MIA PaCa-2 xenograft model was used to image in real time and determine effects on systemic malignant human cancer. Bispecific ligand-directed toxins targeting B cells were used as specificity controls.
resultsDeimmunized EGF4KDEL was significantly effective after systemic injection against established orthotopic MIA PaCa-2 pancreatic cancer and selectively prevented metastasis. Mutagenesis significantly reduced antitoxin levels in vivo with no apparent activity loss in vitro. The drug was effective against 3 human pancreatic cancer lines in vitro, MIA PaCa-2, SW1990, and S2VP10.
conclusionsDespite the metastatic nature of the MIA PaCa-2 orthotopic tumor xenografted in nude mice, high percentages of tumors responded to extended dEGFKDEL treatment resulting in significant anticancer effects and disease-free survivors.
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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.