ReviewJournal of neuro-oncology2003
Interleukin-4-Pseudomonas exotoxin chimeric fusion protein for malignant glioma therapy.
Review in Journal of neuro-oncology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 67 citations in OpenAlex.
- Review
- Convection-enhanced delivery for high-grade glioma.Neuro-oncology practice · 2022Review
- Convection-Enhanced Delivery in Children: Techniques and Applications.Advances and technical standards in neurosurgery · 2022Review
- Combination immunotherapy with IL-4 Pseudomonas exotoxin and IFN-α and IFN-γ mediate antitumor effects in vitro and in a mouse model of human ovarian cancer.Immunotherapy · 2019Article
- Phase I trial of convection-enhanced delivery of IL13-Pseudomonas toxin in children with diffuse intrinsic pontine glioma.Journal of neurosurgery. Pediatrics · 2019Article
- The Process and Regulatory Components of Inflammation in Brain Oncogenesis.Biomolecules · 2017Review
- Interstitial chemotherapy for malignant glioma: Future prospects in the era of multimodal therapy.Surgical neurology international · 2015Article
- Focused ultrasound-induced blood-brain barrier opening to enhance interleukin-12 delivery for brain tumor immunotherapy: a preclinical feasibility study.Journal of translational medicine · 2015Article
- Interleukin-4 receptor alpha overexpression in human bladder cancer correlates with the pathological grade and stage of the disease.Cancer medicine · 2014Article
- Diphtheria toxin-based targeted toxin therapy for brain tumors.Journal of neuro-oncology · 2013Review
- Cytokine patterns in brain tumour progression.Mediators of inflammation · 2013Article
- Convection-enhanced delivery catheter placements for high-grade gliomas: complications and pitfalls.Journal of neuro-oncology · 2012Article
- Challenges in immunotherapy presented by the glioblastoma multiforme microenvironment.Clinical & developmental immunology · 2011Review
- Alternative activation of tumor-associated macrophages by IL-4: priming for protumoral functions.Cell cycle (Georgetown, Tex.) · 2010Review
- Targeted toxins in brain tumor therapy.Toxins · 2010Review
- Experimental approaches for the treatment of malignant gliomas.Pharmacology & therapeutics · 2010Review
- Convection enhanced delivery of boronated EGF as a molecular targeting agent for neutron capture therapy of brain tumors.Journal of neuro-oncology · 2009Article
- Convection-enhanced drug delivery of interleukin-4 Pseudomonas exotoxin (PRX321): increased distribution and magnetic resonance monitoring.The Journal of pharmacology and experimental therapeutics · 2009Article
- Novel drug delivery strategies in neuro-oncology.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2009Review
- Immunotherapeutic approaches for glioma.Critical reviews in immunology · 2009Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human malignant glioma cell lines, primary cell cultures, and tumor specimens derived from surgical samples have been shown to overexpress high-affinity receptors (R) for interleukin-4 (IL-4) in vitro and in situ. The significance of IL-4R expression on malignant glioma cells is still unclear. However, IL-4 has been reported to mediate functional effects in several solid tumor cell lines. These activities include inhibition of cell proliferation, regulation of adhesion molecules, and induction of signal transduction through the JAK/STAT pathway. To target IL-4Rs on tumor cells, we have produced a chimeric recombinant fusion protein consisting of a binding ligand, circularly permuted IL-4 and a mutated form of Pseudomonas exotoxin. This molecule is termed IL4(38-37)-PE38KDEL, cpIL4-PE, or IL-4 cytotoxin. Recombinant cpIL4-PE is highly and specifically cytotoxic to glioma cell lines in vitro, while it is not cytotoxic or less cytotoxic to hematopoietic and normal brain cells. In a nude mouse model, cpIL4-PE showed significant antitumor activity and partial or complete regression of small or large established human glioblastoma tumors. Encouraging preclinical efficacy, safety, and tolerability studies lead to testing of this agent in patients with recurrent glioblastoma. Based on these pilot studies, an extended Phase I/II clinical trial is currently ongoing to determine safety, tolerability, and efficacy of cpIL4-PE when injected stereotactically directly into the recurrent glioma by convection enhanced delivery. Preliminary clinical results suggest that cpIL4-PE can cause pronounced necrosis of recurrent glioma tumors without systemic toxicity. The central nervous system toxicities observed were attributed to the volume of infusion and/or nonspecific toxicity. Ongoing clinical trials will reveal antitumor activities of IL-4 cytotoxin in recurrent malignant glioma.
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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.