Oncolytic Herpes Simplex Virus-1 ONCR-177

**Semantic type:** Pharmacologic Substance|Virus

**Definition:** A recombinant, genetically modified, microRNA (miRNA)-attenuated oncolytic viral strain of the herpes simplex type 1 (HSV-1) virus, with potential oncolytic, immunostimulating and antineoplastic activities. In ONCR-177, a dual bidirectional promoter enables the expression of five different transgenes: the natural killer (NK) cell and T-cell activating cytokine interleuin-12 (IL-12), the chemokines C-C motif chemokine 4 (CCL4) and the extracellular domain of the Fms-related tyrosine kinase 3 ligand (FLT3LG), to allow for expansion and recruitment of classical dendritic cells (DCs), and antagonists to the immune checkpoints programmed cell death protein-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) to counter T cell exhaustion. Upon intra-tumoral administration, the oncolytic HSV-1 ONCR-177 specifically targets, infects and selectively replicates in tumor cells only while not infecting normal, healthy cells. This induces tumor cell lysis. The released virus particles then infect and replicate in neighboring tumor cells, thereby further killing tumor cells. The released tumor-associated antigens (TAAs) from the tumor cells activate the immune system to exert an anti-tumor immune response against the tumor cells, thereby further killing the tumor cells. In addition, the expressed transgenes that are released upon tumor cell lysis induce a systemic tumor-specific immune response and activate NKs, DCs and cytotoxic T-lymphocytes (CTLs) while inhibiting regulatory T-cells (Tregs). This further kills nearby non-infected tumor cells. In ONCR-177, the neurovirulence gene ICP34.5 allows for potent oncolysis, even in the presence of host cell antiviral responses. To ensure selective replication and oncolysis in cancer cells while attenuating replication in healthy tissue, tissue specific miRNA-binding cassettes (miR-T) are inserted into early genes essential for viral replication. In addition, UL37 mutation suppresses latent infection.

**Synonyms:** - ONCR 177 - ONCR-177 - ONCR-177 - ONCR177 - Oncolytic HSV-1 ONCR-177 - oHSV-1 ONCR-177