Making Oncolytic Virotherapy a Clinical Reality: The European Contribution

Oncolytic viruses (OVs) are quickly moving toward the forefront of modern medicines. The reward for the decades of research invested into developing viral platforms that selectively replicate in and lyse tumor cells while sparking anticancer adaptive immunity is presenting in the form of durable therapeutic responses. While this has certainly been a concerted global effort, in this review for the 25th anniversary of the European Society of Gene and Cell Therapy, we focus on the contributions made by European researchers. Research centers across Europe have held central roles in advancing OVs, from the earliest reports of coincidental viral infections leading to antitumor efficacy, to advanced mechanistic studies, and now through Phase I-III trials to imminent regulatory approvals. While challenges still remain, with limitations in preclinical animal models, antiviral immune clearance, and manufacture restrictions enforced by poor viral yields in certain cases, the field has come a very long way in recent years. Thoughtful mechanistic integration of OVs with standard of care strategies and other newly approved therapies should provide potent novel approaches. Combination with immunotherapeutic regimes holds significant promise, and the ability to arm the viral platform with therapeutic proteins for localized expression at the tumor site provides an opportunity for creating highly effective synergistic treatments and brings a new age of targeted cancer therapeutics.