Efficacy and Safety of Oncolytic Viruses Immunotherapy in Advanced Malignancies

AIM: To provide insight into the efficacy and safety of oncolytic viruses (OVs) in advanced malignancies. METHODS: We reviewed 188 clinical trials, including 5410 patients. This review mainly summarized the clinical landscape of OVs, including the immune response, clinical response, and treatment-related adverse events (TRAEs). RESULTS: We found that the most common tumor type targeted was melanoma (1586/541029.3%) and most patients were treated with OVs monotherapy (2893/541053.5%) via intratumoral (2917/541054.4%) or intravenous (1686/541061.2) delivery. Sixty-eight (68/18836.2%) and 74 (74/18836.4%) studies evaluated the tumor microenvironment and systemic immune response, respectively. Importantly, an increase in tumor-specific cytotoxic T lymphocytes was reported in 15 (8.0%) trials. There were 103 (54.8%) and 13 (6.9) studies reporting humoral and cellular virus-specific immune responses, respectively. 129 (129/18868.6%) studies evaluated clinical efficacy in 3536 patients, with objective response and disease control of 870 (24.6%) and 2615 (59.1%), respectively. Subgroup analysis revealed an objective response in 522 (34.5%) and disease control in 953 (62.9%) of the 1514 patients in the herpes simplex virus (HSV) subgroup. The percentages of patients with objective response and disease control for different administration routes, including intratumoral (29.3%; 63.1%) and intravenous (18.1%; 52.8%) injections, and for different treatments including combination (31.8%; 65.1%) and monotherapy (17.3%; 55.1%), were summarized. Immunotherapy may be a promising combination therapy, with objective response and disease control occurring in high proportions of patients (35.9%; 59.9%). Moreover, OVs demonstrated a manageable safety profile, with most TRAEs being Grades 1-2. CONCLUSIONS: This study provides a general overview of the status of OVs clinical trials, but further research is needed to determine the optimal treatment regimen and combination strategy.