ArticleMolecular therapy. Methods & clinical development2015
Preclinical safety and efficacy studies with an affinity-enhanced epithelial junction opener and PEGylated liposomal doxorubicin.
Article in Molecular therapy. Methods & clinical development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 28 citations in OpenAlex.
- Junction opener enables CAR T cell treatment of solid tumors.Scientific reports · 2026Article
- DSG2-Directed CAR-T Cells Safely and Universally Eliminate Solid Tumors.Research square · 2026Article
- The Impact of the Protein-Opener of the Desmoglein Contacts on the Accumulation of Targeted Nanoagents in HER2-Positive Solid Tumors.Doklady. Biochemistry and biophysics · 2025Article
- Article
- Storming the gate: New approaches for targeting the dynamic tight junction for improved drug delivery.Advanced drug delivery reviews · 2023Review
- p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act.Nutrients · 2023Review
- Desmoglein-2 as a cancer modulator: friend or foe?Frontiers in oncology · 2023Review
- Article
- Article
- In vivo HSC transduction in rhesus macaques with an HDAd5/3+ vector targeting desmoglein 2 and transiently overexpressing cxcr4.Blood advances · 2022Article
- Translational development of a tumor junction opening technology.Scientific reports · 2022Article
- Targeting Cancer Cell Tight Junctions Enhances PLGA-Based Photothermal Sensitizers' Performance In Vitro and In Vivo.Pharmaceutics · 2021Article
- Desmoglein-2 as a prognostic and biomarker in ovarian cancer.Cancer biology & therapy · 2020Article
- The Adenovirus Dodecahedron: Beyond the Platonic Story.Viruses · 2020Review
- Structure-based Design of JOC-x, a Conjugatable Tumor Tight Junction Opener to Enhance Cancer Therapy.Scientific reports · 2019Article
- CryoEM structure of adenovirus type 3 fibre with desmoglein 2 shows an unusual mode of receptor engagement.Nature communications · 2019Article
- Designer Oncolytic Adenovirus: Coming of Age.Cancers · 2018Review
- Mapping of Adenovirus of serotype 3 fibre interaction to desmoglein 2 revealed a novel 'non-classical' mechanism of viral receptor engagement.Scientific reports · 2018Article
- Junction opener protein increases nanoparticle accumulation in solid tumors.Journal of controlled release : official journal of the Controlled Release Society · 2018Article
- Desmoglein 2 promotes vasculogenic mimicry in melanoma and is associated with poor clinical outcome.Oncotarget · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
A central treatment resistance mechanism in solid tumors is the maintenance of epithelial junctions between malignant cells that prevent drug penetration into the tumor. We have developed a small recombinant protein (JO-1) that triggers the transient opening of intercellular junctions and thus increases the efficacy of monoclonal antibodies and chemotherapeutic drugs without causing toxicity in mouse tumor models. Here, we provide data toward the clinical translation of an affinity-enhanced version of JO-1, which we call JO-4, in combination with PEGylated liposomal doxorubicin (PLD)/Doxil for ovarian cancer therapy. We have presented X-ray crystallography data suggesting a structural basis for the higher affinity of JO-4 to DSG2. We also confirmed JO-4 efficacy in a xenograft model with primary ovarian cancer cells showing that JO-4 can salvage Doxil therapy when given at a dose that was threefold lower than the therapeutic dose. Furthermore, we tested the safety of intravenous JO-4 alone and in combination with Doxil in Macaca fascicularis, an adequate animal model for predicting toxicity in humans. Our studies did not show critical JO-4-related toxicity or an increase of Doxil-related side effects. Our efficacy and safety data will help to support an Investigational new drug-filing for a JO-4/Doxil combination treatment.
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.