lerapolturev

A recombinant, live attenuated, nonpathogenic oncolytic virus containing the oral poliovirus Sabin type 1 in which the internal ribosomal entry site (IRES) is replaced with the IRES from human rhinovirus type 2 (HRV2), with potential antineoplastic activity. Upon administration of lerapolturev, the poliovirus is selectively taken up by and replicates in tumor cells expressing CD155 (poliovirus receptor, PVR or NECL5) eventually causing tumor cell lysis. Following the lysis of infected cells, the replicated virus is released and can infect adjacent cells, which both induces further tumor cell oncolysis and may activate, through the release of tumor-associated antigens (TAAs) and inflammatory mediators from the lysed tumor cells, the immune system to mount an anti-tumor immune response. This further kills tumor cells. This may also stimulate long-term anti-tumor immunity. Additionally, lerapolturev can induce a systemic anti-tumor immune response through engagement with antigen-presenting cells (APCs) upon CD155 binding thereby further killing tumor cells. CD155, an oncofetal cell adhesion molecule and tumor antigen, is ectopically expressed in certain cancers, such as glioblastoma multiforme (GMB), and plays an important role in tumor cell migration, invasion, and metastasis. Due to the heterologous HRV2 IRES in this recombinant virus, lerapolturev only propagates in susceptible CD155-expressing, nonneuronal neoplastic cells.