Formulation-optimized oncolytic viruses: Advancing systemic delivery and immune amplification.

Cancer is a major global public health challenge. Traditional treatments such as surgery, radiotherapy, and chemotherapy often show limited efficacy, minimal improvements in survival rates, and high recurrence risks. With limited therapeutic options for solid tumors, tumor immunotherapy, which harness the body's immune system, has gained significant attention. Oncolytic viruses (OVs) selectively infect and destroy tumor cells, induce immunogenic cell death (ICD) and stimulate antitumor immune responses. However, current OVs therapies, which are predominantly administered via intratumoral injection, have numerous limitations, including the need for guidance, suboptimal viral spread, extracellular matrix barriers, and immune clearance. These challenges hinder repeated dosing effectiveness and restrict its clinical applicability. Although genetic engineering has improved the tumor selectivity and immune activation of OVs, significant delivery challenges remain. Recently, optimizing pharmaceutical formulations to enhance tumor targeting and viral accumulation has emerged as a key approach to improving OV therapy and expanding clinical applicability. This review highlights the critical role of pharmaceutical formulations in biologics and outlines recent advances in OVs formulations. Specifically, we discuss strategies aimed at enhancing tumor targeting, reducing adverse effects, and promoting antitumor immunity. These strategies significantly enhance OV therapeutic potential and inform novel delivery systems for clinical translation.