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Intranasal Delivery of Therapeutic Stem Cells to Glioblastoma in a Mouse Model
Published on: June 4, 2017
Stem cells as vectors to deliver HSV/tk gene therapy for malignant gliomas
Prakash Rath1, Huidong Shi, Joel A Maruniak
1Division of Biological Sciences, University of Missouri-Columbia, Columbia, MO 65211, USA.
Abstract:
The prognosis of patients diagnosed with malignant gliomas including glioblastoma multiforme (GBM) is poor and there is an urgent need to develop and translate novel therapies into the clinic. Neural stem cells display remarkable tropism toward GBMs and thus may provide a platform to deliver oncolytic agents to improve survival. First we provide a brief review of clinical trials that have used intra-tumoral herpes simplex virus thymidine kinase (HSV/tk) gene therapy to treat brain tumors. Then, we review recent evidence that neural stem cells can be used to deliver HSV/tk to GBMs in animal models. While previous clinical trials used viruses or non-migratory vector-producing cells to deliver HSV/tk, the latter approaches were not effective in humans, primarily because of satellite tumor cells that escaped surgical resection and survived due to low efficiency delivery of HSV/tk. To enhance delivery of HSV/tk to kill gliomas cells, recent animal studies have focused on the ability of neural stem cells, transduced with HSV/tk, to migrate efficiently and selectively to regions occupied by GBM cells. This approach holds the promise of targeting GBM cells that have infiltrated the brain well beyond the original site of the tumor epicenter.
Insights
Neural stem cells offer a promising new way to deliver herpes simplex virus thymidine kinase (HSV/tk) gene therapy directly to glioblastoma multiforme (GBM) tumors. This approach targets invasive cancer cells, potentially improving patient survival rates.
Area of Science:
- Neuro-oncology
- Gene Therapy
- Cancer Therapeutics
Background:
- Malignant gliomas, including glioblastoma multiforme (GBM), have a poor prognosis, necessitating novel therapeutic strategies.
- Current treatments often fail to eradicate invasive tumor cells, leading to recurrence.
Purpose of the Study:
- To review the use of neural stem cells (NSCs) for delivering herpes simplex virus thymidine kinase (HSV/tk) gene therapy to GBM.
- To evaluate the potential of NSCs to overcome limitations of previous GBM treatment approaches.
Main Methods:
- Review of clinical trials involving intra-tumoral HSV/tk gene therapy for brain tumors.
- Examination of preclinical animal models demonstrating NSC-mediated delivery of HSV/tk to GBM.
- Analysis of NSC tropism and migration capabilities towards GBM cells.
Main Results:
- Previous HSV/tk gene therapy trials in humans using viruses or non-migratory cells showed limited efficacy due to inefficient delivery and surviving satellite tumor cells.
- Animal studies show that NSCs transduced with HSV/tk can migrate efficiently and selectively to GBM cells, including those beyond the primary tumor site.
Conclusions:
- Neural stem cells represent a promising platform for targeted delivery of HSV/tk gene therapy in GBM.
- This NSC-mediated approach has the potential to improve treatment outcomes by targeting disseminated GBM cells and enhancing therapeutic delivery.
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