Abstract

BREAKING BARRIERS IN CANCER THERAPY: THE ROLE OF ONCOLYTIC VIRUSES AND THEIR ENGINEERING

Megha Roy, Sukriti Mondal and Jeenatara Begum*

ABSTRACT

Cancer therapy has experienced a shift in paradigm with the discovery of oncolytic viruses (OVs), which aims and kill neoplastic cells preferentially to trigger systemic anti-tumor immunity. This review encompasses the fundamental aspects of oncolytic virotherapy, including viral tropism, tumor-selective replication pathways, and immune-mediated killing of cancer cells. We discuss the pivotal aspects of OV formulation, including delivery strategies to overcome biological barriers such as neutralizing antibodies and the tumor microenvironment. Recent success in genetic engineering has allowed for the development of enhanced OV vectors with immunomodulatory transgenes, tumor-homing ligands, and antiviral defense resistance. Additionally, we discuss the mechanisms of OV degradation, including complement inactivation, phagocytic clearance, and extracellular matrix interaction, impacting therapeutic outcomes. The reviewemphasizes frontier approaches in vector optimization, including synthetic biology, capsid engineering, and combination therapy with checkpoint inhibitors or CAR-T cells. While promising clinical outcomes are reported, there are limitations in systemic delivery, ongoing viral replication, and immunosuppressive tumor evasion. Future areas of research include personalized OV therapies, biomaterial-based delivery vehicles, and AI-driven vector design to maximize tumor specificity and safety. As the field progresses, engineered oncolytic viruses have the gigantic potential to overcome barriers to cancer therapy, offering a versatile platform for precision oncology.

Keywords: Oncolytic Virus, Oncolytic Virotherapy, Viral tropism, Immunotherapy, Viral amplification.