Antitumor activity and reporter gene transfer into @entity35 brain neoplasms inoculated with herpes simplex virus vectors defective in @entity1014 kinase or XXXX reductase.

@entity3038 @entity778 @entity5 @entity1014 @entity35 @entity2151
@entity778 ( @entity778 ) mutants or recombinant vectors might be useful oncolytic agents. Three general types of @entity778 vectors can be potentially used for this purpose: (1) mutants in viral transcription factors, such as ICP0 and ICP4; (2) mutants in enzymes involved in nucleic acid metabolism, such as @entity1014 kinase (TK) and @entity2151 reductase (RR); and (3) mutants in neurovirulence factors, such as gamma 34.5. We tested the destructive ability of each type against @entity35 9L @entity3038 cells in culture. We found that the @entity778 vectors defective in TK or RR were more efficient at @entity5 cell lysis in culture than the other types of @entity778 vectors. This increased efficiency provided the rationale for evaluating the TK and RR mutants in vivo following their stereotactic inoculation into 9L @entity3038 implanted in @entity35 brains. We employed the X-gal enzymatic histochemical assay to show that @entity778 -mediated lacZ gene expression was present in cells within the @entity5 mass in a relatively selective fashion. Immunoreactive @entity778 capsid and core antigens were present both in cells within the @entity5 , as well as in cells such as neurons and astrocytes, directly adjacent to the @entity5 mass. Long-term survival studies revealed that @entity35 treated with either the TK or RR mutant lived significantly longer than control @entity35 (p = 0.014, Kruskal-Wallis one-way analysis of variance). These results indicate that @entity778 vectors, defective in enzymes needed in nucleic acid metabolism, can preferentially mediate lacZ gene expression in cells within the @entity5 . (ABSTRACT TRUNCATED AT 250 WORDS)
