A Chimeric Oncolytic Adenovirus Carried by Macrophages for Glioma Immunotherapy

Purpose: Oncolytic viruses hold promise as a novel frontier in glioma immunotherapy; however, current oncolytic viruses often face challenges of inadequate glioma infiltration and limited viral persistence in clinical settings. Macrophages, with their ability to effectively infiltrate glioma tissue, have emerged as potential cell vectors; however, they naturally resist virus infection. Thus, we constructed oncolytic virus which could be delivered by macrophage carriers. Methods: We engineered a chimeric adenovirus5/35 by cloning the E2F1 promoter and adenovirus E1A gene into an adenovirus5/35 backbone. The virus was then transported by macrophages to the tumor site in xenograft glioma-bearing mice. Results: The genetically engineered adenovirus selectively eradicated tumor cells while sparing normal human cells. The virus efficiently infected macrophages and was effectively delivered to the tumor site. This therapeutic system exhibited robust infiltration of tumor tissue and prolonged the survival of mice. Conclusions: Exploiting macrophage carriers presents a promising approach to enhance the penetration and therapeutic efficacy of oncolytic adenoviruses, holding considerable potential for clinical translation.