Recent progress in the research of suicide gene therapy for malignant glioma

Ryota Tamura, Hiroyuki Miyoshi, Kazunari Yoshida, Hideyuki Okano, Masahiro Toda

Research output: Contribution to journalReview article

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.

Original languageEnglish
JournalNeurosurgical Review
DOIs
Publication statusAccepted/In press - 2019 Jan 1

Fingerprint

Glioma
Genetic Therapy
Suicide
Neural Stem Cells
Research
Clinical Trials
Induced Pluripotent Stem Cells
Mesenchymal Stromal Cells
Ethics
Brain Neoplasms
Genes
Stem Cells
Therapeutics
Bone Marrow
Safety
Cell Line
Survival
Brain
Neoplasms

Keywords

  • 5FC
  • CD
  • GCV
  • HSVtk
  • Neural stem cells
  • Suicide gene therapy

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

Recent progress in the research of suicide gene therapy for malignant glioma. / Tamura, Ryota; Miyoshi, Hiroyuki; Yoshida, Kazunari; Okano, Hideyuki; Toda, Masahiro.

In: Neurosurgical Review, 01.01.2019.

Research output: Contribution to journalReview article

@article{6932cbfae77e4631bd8b98da87575fac,
title = "Recent progress in the research of suicide gene therapy for malignant glioma",
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.",
keywords = "5FC, CD, GCV, HSVtk, Neural stem cells, Suicide gene therapy",
author = "Ryota Tamura and Hiroyuki Miyoshi and Kazunari Yoshida and Hideyuki Okano and Masahiro Toda",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s10143-019-01203-3",
language = "English",
journal = "Neurosurgical Review",
issn = "0344-5607",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - Recent progress in the research of suicide gene therapy for malignant glioma

AU - Tamura, Ryota

AU - Miyoshi, Hiroyuki

AU - Yoshida, Kazunari

AU - Okano, Hideyuki

AU - Toda, Masahiro

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - 5FC

KW - CD

KW - GCV

KW - HSVtk

KW - Neural stem cells

KW - Suicide gene therapy

UR - http://www.scopus.com/inward/record.url?scp=85076116806&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85076116806&partnerID=8YFLogxK

U2 - 10.1007/s10143-019-01203-3

DO - 10.1007/s10143-019-01203-3

M3 - Review article

C2 - 31781985

AN - SCOPUS:85076116806

JO - Neurosurgical Review

JF - Neurosurgical Review

SN - 0344-5607

ER -