How do oncolytic viruses work as cancer therapeutics and what are development considerations?

Oncolytic viruses (OVs) selectively replicate in and lyse tumor cells while stimulating anti-tumor immunity. Mechanisms: 1) Tumor selectivity - through defective interferon responses in tumors, tumor-specific receptors, or engineered selectivity (tissue-specific promoters, microRNA targeting). 2) Direct lysis - replication leads to cell death and release of tumor antigens. 3) Immune activation - danger signals (DAMPs, PAMPs), immunogenic cell death, and tumor antigen presentation generate systemic anti-tumor immunity. Armed OVs: Express cytokines (GM-CSF in T-VEC), checkpoint inhibitors, or bispecific T-cell engagers for enhanced efficacy. Development considerations: pre-existing immunity to viral backbone (HSV, adenovirus); immunogenicity limiting repeated dosing; delivery (intratumoral vs systemic); biodistribution and shedding; manufacturing (high titers, purity, identity testing); combination with checkpoint inhibitors showing promise. FDA-approved: T-VEC (talimogene laherparepvec) for melanoma. Active development in multiple tumor types.