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| Papers |
| Pre-existing herpes simplex virus 1 (HSV-1) immunity decreases, but does not abolish, gene transfer to experimental brain tumors by a HSV-1 vector |
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| U Herrlinger1,2, C M Kramm1,3, K S Aboody-Guterman1, J S Silver4,5, K Ikeda4, K M Johnston6, P A Pechan1, R F Barth7, D Finkelstein8, E A Chiocca4, D N Louis4,5 and X O Breakefield1 |
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1Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA
2Department of Neurology, University of Tuebingen, Germany
3University Children's Hospital, University of Düsseldorf, Germany
4Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA
5Pathology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA
6Department of Neurosurgery, Montreal General Hospital, McGill University, Montreal, Canada
7Department of Pathology, The Ohio State University, Columbus OH, USA
8MGH Cancer Center, Molecular Neurogenetics Unit and Molecular Neuro-Oncology Laboratory, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA
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| Abstract |
| The influence of pre-existing anti-herpes simplex type 1 (HSV-1) immunity on HSV-1 vector-mediated gene transfer to glioma cells was analyzed in this gene marking study using intracranial D74 gliomas in syngeneic Fischer rats. The HSV-1 mutant virus used, hrR3, is defective in ribonucleotide reductase and bears the marker genes E. coli lacZ and HSV-1 thymidine kinase (HSVtk). Initial marker gene expression in tumors 12 h after direct virus injection was reduced in immunized animals to about 15% of that in nonimmunized animals. Marker gene expression in both sets stayed at initial levels for 2 days after intratumoral injection and declined markedly on day 5. Inflammatory infiltrates in the tumor were more prominent in HSV-1-immunized, as compared with nonimmunized animals, at 12 and 24 h, but appeared similar at 2-5 days after injection. By day 10, the immune reaction had subsided in immunized animals and macrophages remained only in nonimmunized animals. In conclusion, gene transfer to brain tumors using a HSV-1 vector was greatly reduced, but not competely abolished, under pre-immunization conditions. Pre-existing antibodies to HSV-1 may also serve a positive role in providing an increased margin of safety in intracranial application of HSV-1 vectors by limiting spread of the virus within the brain and to other tissues. |
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| Keywords |
| HSV-1; immunity; gene transfer; glioma |
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| Received 7 August 1997; accepted 5 January 1998 |
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| June 1998, Volume 5, Number 6, Pages 809-819 |
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