A chimeric oncolytic adenovirus carried by macrophages for glioma immunotherapy

Oncolytic viruses represent a promising frontier in glioma immunotherapy; however, they often encounter challenges, such as inadequate glioma infiltration and limited viral persistence in clinical settings. Macrophages are known to effectively infiltrate glioma tissue and have emerged as potential cell vectors. Nevertheless, they naturally resist viral infection. In this study, we engineered a chimeric adenovirus, OAd5/F35 [E2F1], by incorporating the E2F1 promoter and adenovirus E1A gene into the adenovirus backbone. The virus was then transported by macrophages to the tumor site in xenograft glioma-bearing mice. The genetically engineered adenovirus selectively eradicates tumor cells while sparing normal human cells. Moreover, the virus efficiently infected macrophages and was effectively delivered to the tumor site. This therapeutic system exhibited robust infiltration of tumor tissues and prolonged survival in mice. Exploiting macrophage carriers is a promising approach to enhance the penetration and therapeutic efficacy of oncolytic adenoviruses, with considerable potential for clinical translation.