4613347700

Cancer therapy using oncolytic viruses has gained interest in the last decade. Vesicular stomatitis virus is a well-characterized candidate for this altemative treatment. However, the relative contribution of the antitumoral immune response induced by virotherapy versus the intrinsic oncolytic activity of viruses to the treatment outcome has been difficult to assess. To start addressing this ąuestion, we compared glycoprotein and matrix mutants of VSV, showing different oncolytic potentials for B16/B16gp33 melanoma tumor cells in vitro, with the wild-type virus in their ability to induce tumor-specific CD8⁺ T celi responses and control tumor progression in vivo. Despite the fact that wild-type and G mutants, but not the Mmsir mutant, induced a significant gp33-specific immune response, all VSV strains showed a similar capacity to slow down tumor progression when compared to mock-treated animals. VSV matrix mutant induced the upregulation of MHC-I at the tumor celi surface thus favoring recognition by CD8⁺ T cells. These results demonstrate that VSV mutants affect the induction of an antitumor immune response using several mechanisms. A better understanding of such mechanisms will prove useful for the rational design of viruses with improved therapeutic efficacy.

Key words: oncolytic; VSV; immunotherapy; cytotoxic T cells; melanoma