Abstract

Glioblastoma (GBM) is an aggressive brain tumor with poor prognosis and limited responsiveness to standard therapies. Oncolytic viruses (OVs) offer promise through tumor lysis and immune activation, but clinical efficacy remains limited. In this study, we evaluated the next-generation herpes simplex virus rQNestin34.5v2 as an infected cell vaccine (ICV) platform for GBM immunotherapy. Among a panel of HSV variants screened in the GL261 glioma model, rQNestin34.5v2 demonstrated the strongest induction of interferon-gamma secretion, immunogenic cell death, and dendritic cell activation. In addition, rQNestin34.5v2-ICV induced robust chemokine secretion, including RANTES, IP-10, MIG, and MIP-1α/β, supporting enhanced recruitment of T and NK cells. In vivo, rQNestin34.5v2-ICV elicited antigen-specific T cell responses and complete protection in a prophylactic intracranial GL261 model. In therapeutic settings, a multi-dose ICV regimen significantly prolonged survival resulted in durable responses. These results highlight the potential of rQNestin34.5v2-ICV to bridge innate and adaptive immunity and support its advancement as a clinically translatable immunovirotherapy for GBM. 

Biography

Almohanad Alkayyal is an Associate Professor of Medical Virology at the University of Tabuk, where he also serves as the Director of the Technology Transfer Office (TTO), and an Adjunct Associate Research Scientist in the Immunology Research Program at King Abdullah International Medical Research Centre. He earned his PhD from the University of Ottawa in Canada and completed postdoctoral training in cancer immunotherapy at Harvard Medical School. Currently, he leads a research program focused on developing innovative cancer immunotherapies, particularly oncolytic viruses, cancer vaccines, and cell-based therapeutic platforms.