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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

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
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
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 105 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.
HSV1716, high-grade glioma, clinical trial, viral therapy
398-406
Papanastassiou, V.
77ae3bcc-4b3b-4187-9baf-9627e21b5264
Rampling, R.
15ab64ad-1185-482b-afd6-9f042bc1b4fb
Fraser, M.
525afe70-c2ed-49e4-b46d-3fe44dd2de68
Petty, R.
a24d83a0-4a63-4694-a5af-686dc85107cf
Hadley, D.
5ac4f34c-2186-48e6-986e-d83bc4701a76
Nicoll, J.J.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Mabbs, R.
d3748d65-b2b9-429c-a57a-beebe529c182
Brown, M.
52cf4f52-6839-4658-8cc5-ec51da626049
Papanastassiou, V.
77ae3bcc-4b3b-4187-9baf-9627e21b5264
Rampling, R.
15ab64ad-1185-482b-afd6-9f042bc1b4fb
Fraser, M.
525afe70-c2ed-49e4-b46d-3fe44dd2de68
Petty, R.
a24d83a0-4a63-4694-a5af-686dc85107cf
Hadley, D.
5ac4f34c-2186-48e6-986e-d83bc4701a76
Nicoll, J.J.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Mabbs, R.
d3748d65-b2b9-429c-a57a-beebe529c182
Brown, M.
52cf4f52-6839-4658-8cc5-ec51da626049

Papanastassiou, V., Rampling, R., Fraser, M., Petty, R., Hadley, D., Nicoll, J.J., Mabbs, R. and Brown, M. (2002) 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. Gene Therapy, 9 (6), 398-406. (doi:10.1038/sj/gt/3301664).

Record type: Article

Abstract

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 105 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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More information

Published date: 2002
Keywords: HSV1716, high-grade glioma, clinical trial, viral therapy

Identifiers

Local EPrints ID: 27681
URI: http://eprints.soton.ac.uk/id/eprint/27681
PURE UUID: 48bbef23-4d8a-4d8f-aecf-c13ee752194c
ORCID for J.J. Nicoll: ORCID iD orcid.org/0000-0002-9444-7246

Catalogue record

Date deposited: 25 Apr 2006
Last modified: 16 Mar 2024 03:26

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Contributors

Author: V. Papanastassiou
Author: R. Rampling
Author: M. Fraser
Author: R. Petty
Author: D. Hadley
Author: J.J. Nicoll ORCID iD
Author: R. Mabbs
Author: M. Brown

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