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Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignant glioma

Abstract

The herpes simplex virus (HSV) ICP34.5 null mutant 1716 replicates selectively in actively dividing cells and has been proposed as a potential treatment for cancer, particularly brain tumours. We present a clinical study to evaluate the safety of 1716 in patients with relapsed malignant glioma. Following intratumoural inoculation of doses up to l05 p.f.u., there was no induction of encephalitis, no adverse clinical symptoms, and no reactivation of latent HSV. Of nine patients treated, four are currently alive and well 14–24 months after 1716 administration. This study demonstrates the feasibility of using replication-competent HSV in human therapy.

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Acknowledgements

This work was supported by the UK Medical Research Council project grant No. G9539438N to RR, GC and MB. GMP grade 1716 was generously supplied without charge from Q1 Biotech, Glasgow and we are indebted to David Onions and Gillian Lees for their support. We are grateful to Howard Marsden, MRC Virology Unit, Glasgow who kindly supplied the ZlF11 antibody. Dr A Farrell and Mr E Galloway gave invaluable help and advise with respect to the immunology measurements. We also thank the GTAC committee and the MCA for allowing this study to proceed.

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Rampling, R., Cruickshank, G., Papanastassiou, V. et al. Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignant glioma. Gene Ther 7, 859–866 (2000). https://doi.org/10.1038/sj.gt.3301184

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