To replicate or not to replicate: achieving selective oncolytic virus replication in cancer cells through translational control

Tumor selective replication of Newcastle disease virus: Association with defects of tumor cells in antiviral defence

“…A more detailed discussion about oncolytic viral vectors, mechanisms and recent applications can be found in recent reviews. [49][50][51] We demonstrated that the nontumorigenic cells exert the capability to thwart NDV infection by establishing an early antiviral state that prevents viral genome amplification. This state depends on a strong type-I IFN response and a functional IFN signalling cascade, leading to the activation of multiple defence mechanisms including a fast and sustained production of antiviral proteins.…”

Viruses – seeking and destroying the tumor program

“…HSV-1 and CMV stimulate the phosphorylation of the critical downstream target of mTOR, 4E-BP1, together with the ERK/p38 target mnk-1, which play a pivotal role in enhancing translation and driving viral replication in infected quiescent primary cells (Walsh and Mohr, 2004;Walsh et al, 2005). This is discussed further by (Mohr, 2005). Thus, there are many similarities between virally infected cells and tumor cells in that they both functionally perturb pathways that allow their replication to occur autonomously of extrinsic growth signals.…”

“…Indeed, this is becoming a recurring theme in the development of oncolytic viruses. The oncolytic selectivity of HSV-1 g34.5 mutants, VSV and reovirus is for tumor cells that have deregulated interferon/PKR/Ras-mediated effects on viral RNA translation, again an unanticipated tumor property that is a novel therapeutic target (see Barber, 2005;Mohr, 2005;Shmulevitz et al, 2005).…”

Oncolytic Poliovirus Therapy in a Mouse Model of Neuroblastoma: Preclinical Data Analysis and Future Studies

“…Therefore, we also aimed to develop an immunocompetent animal model that would allow us to investigate the oncolytic capacity of neuroattenuated polioviruses for the treatment of neuroblastoma in the presence of high titers of poliovirus neutralizing antibodies (Toyoda et al, 2007). As shown by us and other investigators, pathogenesis of neurotropic viruses including poliovirus can be controlled by translation (Gromeier et al, 1996(Gromeier et al, , 2000Mohr, 2005). In poliovirus, an exchange of the internal ribosomal entry site (IRES) within the 5'-nontranslated region (NTR) with its counterpart from human rhinovirus type 2 (HRV2), another picornavirus, yielded viruses [called PV1 (RIPO)] that are highly attenuated in mice transgenic for the human poliovirus receptor (PVR) CD155 (CD155 tg mice; Gromeier et al, 1996Gromeier et al, , 1999 yet replicate efficiently and lytically in cell lines derived from malignant glioma and breast cancer (Cello et al, 2008;Gromeier et al, 1996Gromeier et al, , 2000Ochiai et al, 2004Ochiai et al, , 2006.…”