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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
Packer RJ, Raffel C, Villablanca JG, Tonn JC, Burdach SE, Burger K, LaFond D,
McComb JG, Cogen PH, Vezina G, Kapcala LP
Department of Neurology, Children's National Medical Center,
Washington, DC 20010, USA. rpacker@cnmc.org
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 1 (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 HSV-Tk1 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 ependyminomas, 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.
PMID:
10659011 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10659011&dopt=Abstract
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