Assessment of the Novel rVSV-PD-1-4-1BBL Oncolytic Activity on Mouse and Human Cancer Cell Lines.

Background

Oncolytic viruses (OVs), a promising anti-cancer therapeutic, replicate more efficiently in cancer cells rather than in healthy cells due to the alterations in antiviral response mechanisms and dysregulation of signaling pathways. Vesicular stomatitis virus (VSV) is known for low pathogenicity, tropism to various cancer cells, and the ability to lyse cells in the hypoxic tumor microenvironment (TME). Targeted delivery of immune checkpoint and co-stimulatory molecules can enhance the anti-tumor immune response and remodel the immunosuppressive TME. The aim of this study was to compare the activity of rVSV-GFP with rVSV, encoding the programmed cell death protein 1 (PD-1) and tumor necrosis factor ligand superfamily member 9 (4-1BBL).

Methods

The oncolytic efficacy of these rVSV variants used at 105, 106, and 107 TCID50 was evaluated at 24 and 48 h post-infection by flow cytometry in a panel of mouse and human cancer cell lines. Quantitative real-time polymerase chain reaction (qPCR) was used to evaluate mRNA expression levels of certain genes at 12 and 48 h post-infection.

Results

Murine hepatocellular carcinoma (H22) and human melanoma (A375) or human lung carcinoma (A549) were the most sensitive to rVSV therapy cell lines. The higher relative expression of the antiviral response genes RIG-I and IFIT1 within each biological species (mouse or human) correlated with lower sensitivity to rVSV. No such effect was observed for the type I interferons (IFNs), despite their proposed key role in resistance to OV therapy.

Conclusions

H22, A375, and A549 are more susceptible to the oncolytic activity of the novel rVSV-PD-1-4-1BBL.