Cytotoxic and immunogenic mechanisms of recombinant oncolytic poliovirus

•PVSRIPO targets expression of CD155 on tumor and antigen-presenting cells.•PVSRIPO is categorically neuron-incompetent, explaining its attenuation phenotype.•Tumor-specific cytotoxicity is due to unfettered IRES activity in malignant cells.•In situ vaccine effects of viral tumor cytotoxicity and pro-inflammatory activation.

An oncolytic virus (OV) based on poliovirus (PV), the highly attenuated polio/rhinovirus recombinant PVSRIPO, may deliver targeted inflammatory cancer cell killing; a principle that is showing promise in clinical trials for recurrent glioblastoma (GBM). The two decisive factors in PVSRIPO anti-tumor efficacy are selective cytotoxicity and its in situ immunogenic imprint. While our work is focused on what constitutes PVSRIPO cancer cytotoxicity, we are also studying how this engenders host immune responses that are vital to tumor regression. We hypothesize that PVSRIPO cytotoxicity and immunogenicity are inextricably linked in essential, complimentary roles that define the anti-neoplastic response. Herein we delineate mechanisms we unraveled to decipher the basis for PVSRIPO cytotoxicity and its immunotherapeutic potential.