Cancer Viroimmunotherapy Platforms Based on Varicella-Zoster Virus and Cytomegalovirus.

Herpes simplex virus (HSV)-based oncolytic virotherapy has demonstrated promising antitumor effects across various cancer types. However, its application remains limited in scope, and expanding its use to additional cancers poses ongoing challenges. Recently, two other human herpesviruses-varicella-zoster virus (VZV) and cytomegalovirus (CMV)-have emerged as potential platforms for oncolytic virotherapy. In this review, we describe the potential tumor cross-reactivity of the T cell and natural killer (NK) cell responses that are activated and amplified by VZV and CMV, highlighting clinical observations and experimental findings that support the feasibility of redirecting and harnessing these virus-driven immune responses for effective tumor control. We also summarize recent progress in developing oncolytic VZV and CMV vectors, including advances in virus engineering, production, and delivery strategies. This review offers critical insights and highlights key challenges in establishing VZV- and CMV-based cancer viroimmunotherapy platforms.