Evaluation of genetically engineered herpes simplex viruses as oncolytic agents for human malignant brain tumors.

摘要: Earlier studies have shown that genetically engineered herpes simplex viruses ( e.g. , HSV-1) are effective in killing malignant tumor cells both vitro and various murine models. This report focuses on a panel of five viral mutants the γ 134.5 gene, which was previously to cause reduction replication associated neurovirulence HSV. These include R3616, has copies deleted, R4009, stop codon inserted after 28 R849, contains lacZ gene place R908, lacks 41 codons frame 72 R939, carries precluding translation COOH-terminal domain gene. We following: ) all mutant HSVs were avirulent experimental animals but cytotoxic for human vivo ; b - HSV replicated glioma almost as efficiently wild-type HSV-1(F) based assays, situ hybridization DNA, expression infected cell protein 27; c capacity kill derived from glioblastoma multiforme (CH-235MG, D-37MG, D-54MG, D-65MG, U-251MG, U-373MG, SK-MG-1), anaplastic astrocytoma (Hs-683), (U-87MG U-138MG), gliosarcoma (D-32GS), or normal astrocytes demonstrated varied their susceptibility HSV-mediated cytotoxicity cultured two three orders magnitude less susceptible than glia; d scid mice, received 0.5 5 × 106 plaque-forming units either coinoculated at time intracranial transplantation with U251MG D-54MG intratumorally days induction experienced significant increases median survivals, no histopathological indication an infectious encephalitic process. Genetically appear be potentially safe biotherapeutic agent treatment uniformly fatal brain tumors.