Engineering antibody-armed oncolytic viruses: design strategies, synergistic mechanisms, and clinical translation.

Therapeutic antibodies are widely used in cancer biotherapy due to their target specificity, mediating tumor cell inhibition, angiogenesis suppression, and immune modulation. However, systemic administration often leads to off-target effects, as many antibody targets are also expressed in normal tissues, limiting intratumoral drug concentration and causing adverse events. Oncolytic viruses (OVs), which selectively infect and lyse tumor cells while activating host anti-tumor immunity, offer a promising platform for localized antibody delivery. Their inherent tumor tropism, intratumoral administration, and high genetic manipulability enable the engineering of OVs to express exogenous antibodies within the tumor microenvironment, enhancing therapeutic specificity and synergizing oncolytic and immune-mediated effects. In this review, we summarize the biological properties of OVs, strategies for engineering antibody payloads, the mechanistic interplay between OV-induced oncolysis and immune modulation, and current challenges and opportunities for clinical translation. By integrating these aspects, we provide insights into optimizing OV-based antibody therapies for enhanced tumor-targeted efficacy and reduced systemic toxicity.