TY - JOUR
T1 - Treatment of progressive or recurrent pediatric malignant supratentorial brain tumors with herpes simplex virus thymidine kinase gene vector-producer cells followed by intravenous ganciclovir administration
AU - Packer, Roger J.
AU - Raffel, Cory
AU - Villablanca, Judith G.
AU - Tonn, Jörg Christian
AU - Burdach, Stefan E.
AU - Burger, Klaus
AU - LaFond, Deborah
AU - McComb, J. Gordon
AU - Cogen, Philip H.
AU - Vezina, Gilbert
AU - Kapcala, Leonard P.
PY - 2000/2
Y1 - 2000/2
N2 - Object. The outcome for children with recurrent malignant brain tumors is poor. The majority of patients die of progressive disease within months of relapse, and other therapeutic options are needed. The goal of this Phase I study was to evaluate the safety of in vivo suicide gene therapy in 12 children with recurrent, malignant, supratentorial brain tumors. Methods. After optimal repeated tumor resection, multiple injections of murine vector- producing cells shedding murine replication-defective retroviral vectors coding the herpes simplex virus thymidine kinase type I (HSV-Tk1) gene were made into the rim of the resection cavity. Fourteen days after the vector- producing cells were injected, ganciclovir was administered for 14 days. The retroviral vector that was used only integrated and expressed HSVTk1 in proliferating cells, which are killed after a series of metabolic events lead to cell death. The median age of the patients was 11 years (range 2-15 years). Treated brain tumors included seven malignant gliomas, two ependymomas, and three primitive neuroectodermal tumors. The patients were treated with one of three escalating dose concentrations of vector-producer cells. Four transient central nervous system adverse effects were considered possibly related to the vector-producing cells. In no child did permanent neurological worsening or ventricular irritation develop, and tests for replication-competent retroviruses yielded negative findings. Conclusions. This Phase I study demonstrates that in vivo gene therapy in which a replication-defective retroviral vector in murine vector-producing cells is delivered by brain injections can be performed with satisfactory safety in a select group of children with localized supratentorial brain tumors.
AB - Object. The outcome for children with recurrent malignant brain tumors is poor. The majority of patients die of progressive disease within months of relapse, and other therapeutic options are needed. The goal of this Phase I study was to evaluate the safety of in vivo suicide gene therapy in 12 children with recurrent, malignant, supratentorial brain tumors. Methods. After optimal repeated tumor resection, multiple injections of murine vector- producing cells shedding murine replication-defective retroviral vectors coding the herpes simplex virus thymidine kinase type I (HSV-Tk1) gene were made into the rim of the resection cavity. Fourteen days after the vector- producing cells were injected, ganciclovir was administered for 14 days. The retroviral vector that was used only integrated and expressed HSVTk1 in proliferating cells, which are killed after a series of metabolic events lead to cell death. The median age of the patients was 11 years (range 2-15 years). Treated brain tumors included seven malignant gliomas, two ependymomas, and three primitive neuroectodermal tumors. The patients were treated with one of three escalating dose concentrations of vector-producer cells. Four transient central nervous system adverse effects were considered possibly related to the vector-producing cells. In no child did permanent neurological worsening or ventricular irritation develop, and tests for replication-competent retroviruses yielded negative findings. Conclusions. This Phase I study demonstrates that in vivo gene therapy in which a replication-defective retroviral vector in murine vector-producing cells is delivered by brain injections can be performed with satisfactory safety in a select group of children with localized supratentorial brain tumors.
KW - Astrocytoma
KW - Children
KW - Gene therapy
KW - Glioblastoma multiforme
KW - Pediatric brain tumor
KW - Retroviral treatment
UR - http://www.scopus.com/inward/record.url?scp=0033957146&partnerID=8YFLogxK
U2 - 10.3171/jns.2000.92.2.0249
DO - 10.3171/jns.2000.92.2.0249
M3 - Article
C2 - 10659011
AN - SCOPUS:0033957146
SN - 0022-3085
VL - 92
SP - 249
EP - 254
JO - Journal of Neurosurgery
JF - Journal of Neurosurgery
IS - 2
ER -