This study defines the adjuvant and cancer immunotherapy potentials with the recombinant polio-rhinovirus chimera PVSRIPO. This technology has the ability to stimulate an anti-pathogen inflammatory response within the tumor, specifically malignant gliomas, that culminates in dendritic cell and T cell infiltration. This study’s findings show that PVSRIPO functions as a potent intratumor treatment that generates an antigen-specific cytoxic T lymphocyte response.
This study shows that poliovirus can generate antigen-specific CD8 T cells, elicit Th1-promoting inflammation and do not interfere with innate or adaptive immunity. It created a methodology based on the polio-rhinovirus chimera PVSRIPO for a more stable expression of exogenous antigens, showing that PVSRIPO vectors prime antigen-specific CD8 T cells and help them migrate to the tumor site to ultimately delay growth and enhance survival.
This study reviews the role of the constitutive repressor of elF2a phosphorylation (CReP) in translation of poliovirus and the endoplasmic reticulum (ER). CReP anchors the translation machinery at the ER and enables local protein synthesis in this compartment, which is also protected from the suppression of acute stress responses. The study found that partitioning the translation machinery to the ER enables cells to maintain active translation during stress conditions associated with global protein synthesis suppression.
This study conducts a dose-finding and toxicity report in a population of patients with grade IV malignant glioma tumors. It evaluated intra-tumoral delivery of the recombinant polio-rhinovirus chimera (PVSRIPO). The infusion of PVSRIPO did not cause neurovirulent symptoms and the survival rate among patients was higher, with 24 to 36 months compared to the rate among historical control patient populations.