A New Era in Oncology: Clinical Insights Into the Application of Oncolytic Viruses.

When considering treatment-related side effects, cancer therapies often present the most significant severity. Given considerations of safety and efficacy, there is a growing inclination towards biological therapeutic approaches, with Oncolytic Viruses (OVs) emerging as a prominent focus. Initial investigations into OVs commenced with Adenovirus, subsequently leading to the study of other viruses, including Herpes Simplex Virus (HSV), Reovirus, and measles virus, evaluating their potential safety profiles and antitumor efficacy in human subjects. The fundamental principle underlying OV-based cancer therapy lies in harnessing viral infectivity and immunogenicity, which are engineered for selective targeting of tumor cells. Following the US Food and Drug Administration (FDA) approval of the HSV-based therapy (T-VEC) for Melanoma, interest in exploring other viral platforms for the potential treatment of various cancer types has notably expanded. A considerable number of OVs have progressed to various stages of clinical evaluation. This review provides an in-depth examination of OV classification, mechanisms of action, delivery strategies, and crucial genetic modifications, furthermore summarizing data from pivotal trials to underscore the efficacy and advancement of OVs from investigational modalities to clinical implementation. For the scope of this review, clinical trial data spanning the past 11 years (2013 to 2024) were accessed from ClinicalTrials.gov and further categorized according to their ongoing clinical trial phases and their utilization in combination with Immune Checkpoint Inhibitors (ICI) or other established therapies. In summary, this work presents a comprehensive overview of recent developments within the field of cancer therapy, specifically concerning Oncolytic Viruses.