title: Gene therapy for mice sarcoma with oncolytic herpes simplex virus-1 lacking the apoptosis-inhibiting gene, icp34.5.
abstract: A mutant herpes simplex virus 1, mtHSV, was constructed by inserting the E. coli beta-galactosidase gene into the loci of icp34.5, the apoptosis-inhibiting gene of HSV. The mtHSV replicated in and lysed U251 (human glioma cells), EJ (human bladder cells), and S-180 (mice sarcoma cells), but not Wish (human amnion cells) cells. With its intact tk (thymidine kinase) gene, mtHSV exhibited susceptibility to acyclovir (ACV), which provided an approach to control viral replication. An in vivo test with mtHSV was conducted in immune-competent mice bearing sarcoma S-180 tumors, which were treated with a single intratumoral injection of mtHSV or PBS. Tumor dimensions then were measured at serial time points, and the tumor volumes were calculated. Sarcoma growth was significantly inhibited with prolonged time and reduced tumor volume. There was microscopic evidence of necrosis of tumors in treated mice, whereas no damage was found in other organs. Immunohistochemical staining revealed that virus replication was exclusively confined to the treated tumor cells. HSV-1 DNA was detected in tumors, but not in the other organs by a polymerase chain reaction analysis. From these experiments, we concluded that mtHSV should be a safe and promising oncolytic agent for cancer treatment.
authors.affiliation: Institute of Virology, Wuhan University, Wuhan 430072, P. R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Lan
authors.forename: Changyuan
authors.initials: C
authors.lastname: Dong
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Qi
authors.forename: Gengfu
authors.initials: G
authors.lastname: Xiao
authors.forename: Feng
authors.initials: F
authors.lastname: Xue
mesh_terms: D000212:Acyclovir / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D017209:Apoptosis; D002460:Cell Line; D045744:Cell Line, Tumor; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009336:Necrosis; D009368:Neoplasm Transplantation; D012510:Sarcoma 180 / Q000473:pathology / Q000628:therapy* / Q000821:virology; D013937:Thymidine Kinase / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D014764:Viral Proteins; C066469:gamma 34.5 protein, Human herpesvirus 1; D013937:Thymidine Kinase; D000212:Acyclovir