*4.7. Oncolytic Poliovirus*

Poliovirus is an enterovirus in the Picornaviridae family of single-stranded RNA vi-ruses. A non-pathogenic oncolytic variant was engineered by replacing the internal ribo-somal entry site (IRES) of the poliovirus type 1 (Sabin) vaccine strain with the human rhi-novirus type 2 IRES (PVS-RIPO). The affinity of poliovirus for its cellular receptor CD155, which is upregulated on GBM cells, provides a unique opportunity target these tumors [16]. This approach demonstrated potent anti-glioma activity in mouse models and led to translation to clinical investigation for GBM [17,148]. Impressive results were obtained in a clinical phase II trial testing the recombinant nonpathogenic polio–rhinovirus chimera (PVSRIPO), oncolytic virus in 61 patients with recurrent GBM. Twenty-one percent of patients were still alive 36 months after initiation of treatment [149]. The source of this striking response in a subgroup of patients has yet to be elucidated. However, intriguingly, transcriptomic analysis revealed a correlation between low tumor mutational burden, tumor-intrinsic inflammation, and improved survival after PVSRIPO or anti-PD1 immunotherapy in recurrent GBM patients [150]. Further studies are required to confirm whether these characteristics hold predictive biomarker potential.
