drug_type
RELEVANT_DRUG
intervention_type
Oncolytic viral immunotherapy
drug_description
Oncolytic viral immunotherapy (PVSRIPO), a live-attenuated poliovirus type 1 Sabin/rhinovirus chimera that targets CD155/Necl-5 on tumor and antigen-presenting cells, replicates to cause oncolysis and antigen release, and induces type I IFN and dendritic-cell activation to drive tumor-specific T-cell responses.
nci_thesaurus_concept_id
C184921
nci_thesaurus_preferred_term
Lerapolturev
nci_thesaurus_definition
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.
drug_category
ONCOLYTIC VIRUS
drug_class
Gene therapy
drug_delivery_route
Intracerebral (via convection-enhanced delivery), Subcutaneous
drug_mechanism_of_action
Live-attenuated poliovirus type 1 Sabin/human rhinovirus HRV2 IRES chimera that targets CD155 (Necl-5) on tumor and antigen-presenting cells; selectively replicates in CD155+ nonneuronal tumor cells causing oncolysis and antigen release, which triggers type I interferon signaling and dendritic-cell activation to drive tumor-specific T-cell responses and systemic antitumor immunity.
drug_name
Lerapolturev
nct_id_drug_ref
NCT06177964