Repeated dosing improves oncolytic rhabdovirus therapy in mice via interactions with intravascular monocytes

• DOI: 10.1038/s42003-022-04254-3
• Publication Date: 2022-12-19T05:02:41Z
• Authors: Victor Naumenko; Jahanara Rajwani; Madison Turk; Chunfen Zhang; Mandy Tse; Rachelle P. Davis; Daesun Kim; Andrea Rakic; Himika Dastidar; Shinia Van; Laura K. Mah; Esha K. Kaul; Vladimir P. Chekh...; Douglas J. Mahoney; Craig N. Jenne
• Keywords: Oncolytic Virotherapy; 0301 basic medicine; 0303 health sciences; QH301-705.5; Article; Monocytes; 3. Good health; Mice; Oncolytic Viruses; 03 medical and health sciences; Neoplasms; Tumor Microenvironment; Animals; Biology (General); Rhabdoviridae

AbstractThere is debate in the field of oncolytic virus (OV) therapy, whether a single viral dose, or multiple administrations, is better for tumor control. Using intravital microscopy, we describe the fate of vesicular stomatitis virus (VSV) delivered systemically as a first or a second dose. Following primary administration, VSV binds to the endothelium, initiates tumor infection and activates a proinflammatory response. This initial OV dose induces neutrophil migration into the tumor and limits viral replication. OV administered as a second dose fails to infect the tumor and is captured by intravascular monocytes. Despite a lack of direct infection, this second viral dose, in a monocyte-dependent fashion, enhances and sustains infection by the first viral dose, promotes CD8 T cell recruitment, delays tumor growth and improves survival in multi-dosing OV therapy. Thus, repeated VSV dosing engages monocytes to post-condition the tumor microenvironment for improved infection and anticancer T cell responses. Understanding the complex interactions between the subsequent viral doses is crucial for improving the efficiency of OV therapy and virus-based vaccines.