RESUMEN
Oncolytic virotherapy is a new and safe therapeutic strategy based on the inherent cytotoxicity of oncolytic viruses and their ability to replicate and spread within tumors in a selective manner. In a previous study, a new type of oncolytic herpes simplex virus type 2 (oHSV-2, named OH2) was constructed to treat human cancers. That study demonstrated that OH2 is genetically and biologically stable. Its antitumor activity was maintained, even after passaging the virus for >20 generations. To advance OH2 into a clinical trial, a systematic preclinical safety evaluation was performed, which included: an acute toxicity test of OH2 in BALB/c mice; repeated dose toxicity tests of OH2 in BALB/c mice and cynomolgus monkeys; and biodistribution assays of OH2 in BALB/c mice, tumor-bearing mice, tumor-bearing nude mice, and cynomolgus monkeys. The results of this preclinical safety evaluation of OH2 indicate that OH2 is safe and suitable for clinical trials.
Asunto(s)
Vectores Genéticos/genética , Herpesvirus Humano 2/genética , Viroterapia Oncolítica , Virus Oncolíticos/genética , Animales , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Femenino , Terapia Genética , Vectores Genéticos/administración & dosificación , Vectores Genéticos/efectos adversos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/sangre , Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Cobayas , Hemólisis , Herpesvirus Humano 2/inmunología , Humanos , Macaca fascicularis , Masculino , Ratones , Ratones Endogámicos BALB C , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/patología , Neoplasias/terapia , Virus Oncolíticos/inmunología , Distribución Tisular , Transgenes , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Oncolytic virotherapy is a new therapeutic strategy based on the inherent cytotoxicity of viruses and their ability to replicate and spread in tumors in a selective manner. We constructed a new type of oncolytic herpes simplex virus type 2 (oHSV-2, named OH2) to treat human cancers, but a systematic evaluation of the stability and oncolytic ability of this virus is lacking. In this study, we evaluated its physical stability, gene modification stability and biological characteristics stability, including its anti-tumor activity in an animal model. The physical characteristics as well as genetic deletions and insertions in OH2 were stable, and the anti-tumor activity remained stable even after passage of the virus for more than 20 generations. In conclusion, OH2 is a virus that has stable structural and biological traits. Furthermore, OH2 is a potent oncolytic agent against tumor cells.