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Published on: September 1, 2018
Recent progress in the research of suicide gene therapy for malignant glioma
Ryota Tamura1, Hiroyuki Miyoshi2, Kazunari Yoshida1
1Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Abstract:
Malignant glioma, which is characterized by diffuse infiltration into the normal brain parenchyma, is the most aggressive primary brain tumor with dismal prognosis. Over the past 40 years, the median survival has only slightly improved. Therefore, new therapeutic modalities must be developed. In the 1990s, suicide gene therapy began attracting attention for the treatment of malignant glioma. Some clinical trials used a viral vector for suicide gene transduction; however, it was found that viral vectors cannot cover the large invaded area of glioma cells. Interest in this therapy was recently revived because some types of stem cells possess a tumor-tropic migratory capacity, which can be used as cellular delivery vehicles. Immortalized, clonal neural stem cell (NSC) line has been used for patients with recurrent high-grade glioma, which showed safety and efficacy. Embryonic and induced pluripotent stem cells may be considered as sources of NSC because NSC is difficult to harvest, and ethical issues have been raised. Mesenchymal stem cells are alternative candidates for cellular vehicle and are easily harvested from the bone marrow. In addition, a new type of nonlytic, amphotropic retroviral replicating vector encoding suicide gene has shown efficacy in patients with recurrent high-grade glioma in a clinical trial. This replicating viral capacity is another possible candidate as delivery vehicle to tackle gliomas. Herein, we review the concept of suicide gene therapy, as well as recent progress in preclinical and clinical studies in this field.
Insights
Suicide gene therapy offers new hope for malignant glioma treatment. Stem cells and novel viral vectors show promise for delivering therapeutic genes to brain tumors, improving patient outcomes.
Area of Science:
- Neuro-oncology
- Gene Therapy
- Stem Cell Biology
Background:
- Malignant glioma is an aggressive brain tumor with poor prognosis and limited treatment options.
- Traditional therapies struggle to address diffuse tumor infiltration.
- Suicide gene therapy has re-emerged as a promising treatment strategy.
Purpose of the Study:
- To review the concept of suicide gene therapy for malignant glioma.
- To discuss recent advancements in preclinical and clinical applications.
- To explore novel delivery vehicles for gene therapy.
Main Methods:
- Review of existing literature on suicide gene therapy for glioma.
- Analysis of viral vector-based gene delivery systems.
- Evaluation of stem cell-based delivery vehicles, including neural stem cells (NSCs), embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells.
- Examination of replicating viral vectors for gene transduction.
Main Results:
- Viral vectors have limitations in covering extensive glioma infiltration.
- Stem cells, particularly NSCs, demonstrate tumor-tropic migration for targeted delivery.
- Clinical trials show safety and efficacy of NSC-based therapy for recurrent high-grade glioma.
- Novel replicating viral vectors also show efficacy in clinical trials.
- Alternative stem cell sources and advanced viral vectors are being investigated.
Conclusions:
- Suicide gene therapy, utilizing stem cells or advanced viral vectors, presents a viable strategy for malignant glioma.
- Targeted delivery systems are crucial for overcoming treatment challenges.
- Ongoing research focuses on optimizing delivery vehicles and therapeutic efficacy.
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