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- Title
Repeated dosing improves oncolytic rhabdovirus therapy in mice via interactions with intravascular monocytes.
- Authors
Naumenko, Victor; Rajwani, Jahanara; Turk, Madison; Zhang, Chunfen; Tse, Mandy; Davis, Rachelle P.; Kim, Daesun; Rakic, Andrea; Dastidar, Himika; Van, Shinia; Mah, Laura K.; Kaul, Esha K.; Chekhonin, Vladimir P.; Mahoney, Douglas J.; Jenne, Craig N.
- Abstract
There 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. A secondary (but not primary) dose of the oncolytic virus, VSV, is captured by monocytes and promotes CD8 + T cell recruitment, thereby revealing a mechanism underlying the clinical benefit of repeat dosing in oncolytic virus therapy.
- Subjects
MONOCYTES; ONCOLYTIC virotherapy; VESICULAR stomatitis; TUMOR growth; TUMOR microenvironment; NEUTROPHILS
- Publication
Communications Biology, 2022, Vol 5, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-022-04254-3