title: Oncolytic Sindbis virus targets tumors defective in the interferon response and induces significant bystander antitumor immunity in vivo.
abstract: Sindbis virus (SBV) has been shown to possess oncolytic potential in many human xenograft tumor models in immunocompromised mice. However, the mechanism underlying the tumor selectivity of SBV remains undetermined. In this study, we provide evidence that the tumor tropism of SBV infection is not determined by the levels of SBV receptor but by the status of the type I interferon (IFN) response in the tumors. Our results demonstrate that cells with defects in the IFN response (in either IFN-β production or IFN signaling) were highly susceptible to SBV infection in vitro. The results of oncolysis experiments conducted in immunocompetent animals further confirmed that the success of SBV-mediated oncolysis is greatly dependent on the presence of defects in IFN signaling in tumors. In all cases, viral titers rapidly declined in tumors due to host immune responses in immunocompetent animals. Interestingly, however, tumor-specific immune responses were concomitantly elicited, which might contribute to the sustained antitumor effect observed after the clearance of SBV. These findings indicate that SBV-mediated virotherapy is a promising therapeutic strategy for cancers defective in the IFN response and underscore the importance of bystander antitumor immunity in the efficacy of this virotherapy.
authors: Graduate Institute of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Pong-Yu
authors: PY
authors: Huang
authors: Jih-Huong
authors: JH
authors: Guo
authors: Lih-Hwa
authors: LH
authors: Hwang
mesh_terms: D000818:Animals; D024201:Bystander Effect / Q000276:immunology*; D002460:Cell Line; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007372:Interferons / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics* / Q000502:physiology; D011991:Receptors, Virus / Q000378:metabolism; D015398:Signal Transduction; D012845:Sindbis Virus / Q000235:genetics* / Q000502:physiology; D056189:Viral Tropism
chemical_list: D011991:Receptors, Virus; D016899:Interferon-beta; D007372:Interferons