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Updated: Jun 19, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Stem cells as delivery vehicles for oncolytic adenoviral virotherapy
Justin Kranzler1, Matthew A Tyler, Adam M Sonabend
1The Brain Tumor Center, The University of Chicago, Pritzker School of Medicine, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
Abstract:
Glioblastoma multiforme is the most common primary intracranial tumor in humans. Despite continued advances in cancer therapy, the outcome for patients diagnosed with this disease remains bleak. Novel treatments involving the use of conditionally replicating adenoviruses (CRAds) to target malignant brain tumors have undergone extensive research and proven to be a promising mode of glioblastoma therapy. CRAds are genetically manipulated to replicate within tumor cells, exhibiting a high degree of infectivity, cytotoxicity, and transgene expression. While the use of various CRAds has been deemed safe for intracranial injection in preclinical trials, a significant therapeutic effect has yet to be seen in patients. This shortcoming stems from the distribution limitations involved with local delivery of virolytic agents. To enhance this modality of treatment, stem cells have been explored as cellular vehicles in virotherapy applications, given that they possess an intrinsic tropism for malignant brain tumors. Stem cell loaded CRAd delivery offers a more specific and effective method of targeting disseminated tumor cells and forms the basis for this review.
Insights
Conditionally replicating adenoviruses (CRAds) show promise for glioblastoma therapy but face delivery challenges. Using stem cells to deliver CRAds enhances targeting of brain tumors for improved glioblastoma treatment.
Area of Science:
- Oncology
- Virology
- Neuroscience
Background:
- Glioblastoma multiforme is a prevalent and aggressive primary brain tumor with poor patient outcomes.
- Current cancer therapies offer limited success for glioblastoma patients.
- Conditionally replicating adenoviruses (CRAds) are engineered viruses showing potential for glioblastoma therapy due to tumor-specific replication and cytotoxicity.
Purpose of the Study:
- To review the potential of stem cells as delivery vehicles for CRAds in glioblastoma virotherapy.
- To address the limitations of local CRAd delivery for widespread tumor targeting.
Main Methods:
- Review of preclinical and clinical studies on CRAd therapy for glioblastoma.
- Exploration of stem cell tropism towards malignant brain tumors.
- Analysis of stem cell-mediated CRAd delivery systems.
Main Results:
- CRAds demonstrate safety in preclinical intracranial injections and exhibit infectivity, cytotoxicity, and transgene expression in tumor cells.
- Local delivery of CRAds is limited in effectively reaching disseminated tumor cells.
- Stem cells possess an inherent ability to migrate towards and infiltrate brain tumors.
Conclusions:
- Stem cell-loaded CRAd delivery presents a promising strategy to overcome distribution limitations of virotherapy.
- This approach offers enhanced specificity and efficacy for targeting disseminated glioblastoma cells.
- Stem cell-mediated virotherapy holds potential for improved glioblastoma treatment outcomes.
