Selective oncotropism and cytolytic activity against tumors have made certain viruses subject to investigation as novel treatment modalities. However, monotherapy with oncolytic viruses (OVs) has shown limited success and modest clinical benefit. The capacity to genetically engineer OVs makes them a desirable platform to design complementary treatment modalities to overcome the existing treatment options' shortcomings. In recent years, our knowledge of interactions of the tumors with the immune system has expanded profoundly. There is a growing body of literature supporting immunomodulatory roles for OVs. The concept of bioengineering these platforms to induce the desired immune response and complement the current immunotherapeutic modalities to make immune-resistant tumors responsive to immunotherapy is under investigation in preclinical and early clinical trials. This review provides an overview of attempts to optimize oncolytic virotherapy as essential components of the multimodality anticancer therapeutic approach and discusses the challenges in translation to clinical practice.
© 2021 by American Society of Clinical Oncology.