Abstract

ONCR-177, A miR-Attenuated Oncolytic HSV-1 for Potent Activation of Anti-Tumor Immunity

Lorena Lerner, Vice President, Molecular Biology & Virology, Oncorus

Oncolytic viruses (OVs) represent a new class of therapeutic agents for the treatment of cancers that poorly respond to immune checkpoint inhibitors. OV promote anti-tumor responses by a dual mechanism of action: the selective oncolysis of tumor cells, followed by the development of systemic anti-tumor immune responses.

Oncorus has developed a robust OV platform, including a novel approach to maintain safety while enhancing oncolytic potency by leveraging the differential expression of micro-RNA (miR) technology to deliver multiple warheads in a single injection. ONCR-177, a highly engineered recombinant oncolytic Herpes Simplex Virus (oHSV), expresses transgenes which can potently activates local and systemic anti-tumor immune response. ONCR-177, or its mouse surrogate virus mONCR-171, was tested in a series of experiments designed to characterize its biodistribution, anti-tumor activity, and mechanisms of action. ONCR-177/mONCR-171 potently activates local and systemic anti-tumor immune responses that result in durable responses, extended survival, and the elicitation of protective immunity.  These encouraging preclinical data warrant the clinical investigation of ONCR-177 in patients with metastatic cancer.