1. Real-time monitoring of oncolytic VSV properties in a novel in vitro microphysiological system containing 3D multicellular tumor spheroids.
- Author
-
Lee KJ, Lee SW, Woo HN, Cho HM, Yu DB, Jeong SY, Joo CH, Jeong GS, and Lee H
- Subjects
- A549 Cells, Cell Culture Techniques methods, Drug Screening Assays, Antitumor methods, Extracellular Matrix, Human Umbilical Vein Endothelial Cells, Humans, Neoplasms immunology, Oncolytic Viruses genetics, Spheroids, Cellular, Vesiculovirus genetics, Neoplasms therapy, Oncolytic Virotherapy, Oncolytic Viruses immunology, Vesiculovirus immunology
- Abstract
As a new class of cancer therapeutic agents, oncolytic viruses (OVs) have gained much attention not only due to their ability to selectively replicate in and lyse tumor cells, but also for their potential to stimulate antitumor immune responses. As a result, there is an increasing need for in vitro modeling systems capable of recapitulating the 3D physiological tumor microenvironment. Here, we investigated the potential of our recently developed microphysiological system (MPS), featuring a vessel-like channel to reflect the in vivo tumor microenvironment and serving as culture spaces for 3D multicellular tumor spheroids (MCTSs). The MCTSs consist of cancer A549 cells, stromal MRC5 cells, endothelial HUVECs, as well as the extracellular matrix. 3D MCTSs residing in the MPS were infected with oncolytic VSV expressing GFP (oVSV-GFP). Post-infection, GFP signal intensity increased only in A549 cells of the MPS. On the other hand, HUVECs were susceptible to virus infection under 2D culture and IFN-β secretion was quite delayed in HUVECs. These results thus demonstrate that OV antitumoral characteristics can be readily monitored in the MPS and that its behavior therein somewhat differs compared to its activity in 2D system. In conclusion, we present the first application of the MPS, an in vitro model that was developed to better reflect in vivo conditions. Its various advantages suggest the 3D MCTS-integrated MPS can serve as a first line monitoring system to validate oncolytic virus efficacy., Competing Interests: The authors declare no competing interests.
- Published
- 2020
- Full Text
- View/download PDF