ArticleMolecular therapy oncolytics2017
Optimization of a Neural Stem-Cell-Mediated Carboxylesterase/Irinotecan Gene Therapy for Metastatic Neuroblastoma.
Article in Molecular therapy oncolytics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
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- Converging frontiers in cancer treatment: the role of nanomaterials, mesenchymal stem cells, and microbial agents-challenges and limitations.Discover oncology · 2024Review
- Cell and gene therapy in neuro-oncology.Handbook of clinical neurology · 2024Review
- Neuroprotective potential of intranasally delivered L-myc immortalized human neural stem cells in female rats after a controlled cortical impact injury.Scientific reports · 2023Article
- Gene Therapy for High Grade Glioma: The Clinical Experience.Expert opinion on biological therapy · 2023Review
- Intravenously Infused Stem Cells for Cancer Treatment.Stem cell reviews and reports · 2021Review
- Development of next-generation tumor-homing induced neural stem cells to enhance treatment of metastatic cancers.Science advances · 2021Article
- Heterogenous chemosensitivity of a panel of organoid lines derived from small cell neuroendocrine carcinoma of the uterine cervix.Human cell · 2021Article
- Treating Metastatic Brain Cancers With Stem Cells.Frontiers in molecular neuroscience · 2021Review
- Recent Progress of Stem Cell Therapy in Cancer Treatment: Molecular Mechanisms and Potential Applications.Cells · 2020Review
- Development of a Split Esterase for Protein-Protein Interaction-Dependent Small-Molecule Activation.ACS central science · 2019Article
- Concise Review: Neural Stem Cell-Mediated Targeted Cancer Therapies.Stem cells translational medicine · 2018Review
- GMP Production and Scale-Up of Adherent Neural Stem Cells with a Quantum Cell Expansion System.Molecular therapy. Methods & clinical development · 2018Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
Despite improved survival for children with newly diagnosed neuroblastoma (NB), recurrent disease is a significant problem, with treatment options limited by anti-tumor efficacy, patient drug tolerance, and cumulative toxicity. We previously demonstrated that neural stem cells (NSCs) expressing a modified rabbit carboxylesterase (rCE) can distribute to metastatic NB tumor foci in multiple organs in mice and convert the prodrug irinotecan (CPT-11) to the 1,000-fold more toxic topoisomerase-1 inhibitor SN-38, resulting in significant therapeutic efficacy. We sought to extend these studies by using a clinically relevant NSC line expressing a modified human CE (hCE1m6-NSCs) to establish proof of concept and identify an intravenous dose and treatment schedule that gave maximal efficacy. Human-derived NB cell lines were significantly more sensitive to treatment with hCE1m6-NSCs and irinotecan as compared with drug alone. This was supported by pharmacokinetic studies in subcutaneous NB mouse models demonstrating tumor-specific conversion of irinotecan to SN-38. Furthermore, NB-bearing mice that received repeat treatment with intravenous hCE1m6-NSCs and irinotecan showed significantly lower tumor burden (1.4-fold, p = 0.0093) and increased long-term survival compared with mice treated with drug alone. These studies support the continued development of NSC-mediated gene therapy for improved clinical outcome in NB patients.
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