Key result
Intracerebral inoculation of PVS(RIPO) in CD155 transgenic mice demonstrated a temperature-sensitive phenotype and genetic stability in the CNS, supporting its safety for human gliomas.
The recombinant oncolytic poliovirus PVS(RIPO) demonstrates genetic stability and neuroattenuation in a transgenic mouse model, supporting its safety for potential use in human glioma treatment.
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Supports PVS(RIPO) preclinical safety for gliomas; leaves open translation to human trials.
The use of oncolytic recombinant polioviruses has an important therapeutic potential in the treatment of human gliomas. This study was carried out to assess parameters of the utility of the oncolytic poliovirus/human rhinovirus type 2 chimeras (PV/HRV2). The prototype PV/HRV2 chimera was constructed containing the complete genome of wild-type PV type 1 (Mahoney) [PV1(M)] in which the cognate IRES was replaced with that of HRV2 [called PV1(RIPO)]. A derivative of PV1(RIPO) is PV1(RIPOS) in which the capsid coding region (P1) was replaced with the capsid-coding region of the PV type 1 (Sabin) [PV1(S)] vaccine strain. In addition, a third PV/HRV2 chimera was constructed containing the complete genome of PV1(S) in which the cognate IRES was replaced with that of HRV2 [termed PVS(RIPO)]. To analyze the growth phenotypes of PV/HRV2 recombinants [PV1(RIPO), PV1(RIPOS), PVS(RIPO)], one-step growth experiments were performed in four human cell lines at three different temperatures. To address the safety profile, PVS(RIPO) was injected into the brain of CD155 tg mice at the dose 10(7) PFU. Then, clinical signs, persistence of the virus in the CNS and genetic stability of PVS(RIPO) replicating in the CNS were evaluated. The data obtained in the present study suggest (i) a correlation between temperature-sensitive (ts) phenotype in both neuronal and non-neuronal cell lines and neuroattenuation in experimental animals, (ii) that PVS (RIPO) is genetically stable on replication in the CNS of poliovirus-susceptible mice. These findings highlight the safety of intracerebral inoculation of PVS(RIPO) for the treatment of human glioma.
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Cello et al. (2007) studied human gliomas. PVS(RIPO) and other PV/HRV2 chimeras was evaluated on growth phenotypes, clinical signs, persistence in CNS, and genetic stability. Intracerebral inoculation of PVS(RIPO) in CD155 transgenic mice demonstrated a temperature-sensitive phenotype and genetic stability in the CNS, supporting its safety for human gliomas.
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