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The potential for efficacy of the
modified (ICP 34.5(-)) herpes simplex virus HSV1716 following
intratumoural injection into human malignant glioma: a proof of
principle study
Papanastassiou V, Rampling R, Fraser M, Petty
R, Hadley D, Nicoll J, Harland J, Mabbs R,
Brown M
Department of Neurosurgery, University of Glasgow, Institute of
Neurological Sciences, Southern General Hospital, Glasgow, UK.
We have previously demonstrated the safety of intratumoural
administration of the selectively replication-competent herpes simplex
virus mutant HSV1716 in patients with high-grade glioma (HGG).
Here we show its potential for efficacy by
demonstrating that the virus survives and replicates when injected
into the tumours of patients.
Since HSV replication is a cytolytic
process it must result in tumour cell killing.
Twelve patients with
biopsy-verified HGG received an intratumoural injection of 10(5)
plaque-forming units (p.f.u.) of HSV1716.
Four to 9 days after
inoculation, tumours were removed and assayed for evidence of viral
replication.
In two patients, HSV1716, in excess of the input dose was
recovered from the injection site.
HSV DNA was detected by PCR at the
sites of inoculation in 10 patients and at distal tumour sites in four.
HSV-specific antigen was detected in tumour tissue from two patients.
In five patients an immunological response to HSV1716, as detected by
changes in levels of IgG and IgM, was demonstrated.
This study
demonstrates that HSV1716 replicates in HGG without causing toxicity
in both HSV-seropositive and -seronegative patients.
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