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.
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 completely 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.
Herrlinger
U
U
Neurology, MGH Cancer Center, Massachusetts General Hospital, Charlestown 02129, USA.
Kramm
C M
CM
Aboody-Guterman
K S
KS
Silver
J S
JS
Ikeda
K
K
Johnston
K M
KM
Pechan
P A
PA
Barth
R F
RF
Finkelstein
D
D
Chiocca
E A
EA
Louis
D N
DN
Breakefield
X O
XO
D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005819:Genetic Markers; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D005910:Glioma / Q000276:immunology / Q000628:therapy*; D007114:Immunization; D051381:Rats; D011916:Rats, Inbred F344; D018139:Simplexvirus / Q000276:immunology*; D013997:Time Factors
D005819:Genetic Markers