TLR4-mediated immunomodulatory properties of the bacterial metalloprotease arazyme in preclinical tumor models.

ABSTRACT: Despite the recent approval of new agents for metastatic melanoma, its treatment remains challenging. Moreover, few available immunotherapies induce a strong cellular immune response, and selection of the correct immunoadjuvant is crucial for overcoming this obstacle. Here, we studied the immunomodulatory properties of arazyme, a bacterial metalloprotease, which was previously shown to control metastasis in a murine melanoma B16F10-Nex2 model. The antitumor activity of arazyme was independent of its proteolytic activity, since heat-inactivated protease showed comparable properties to the active enzyme; however, the effect was dependent on an intact immune system, as antitumor properties were lost in immunodeficient mice. The protective response was IFNγ-dependent, and CD8(+) T lymphocytes

SUBMITTER: Pereira FV 

PROVIDER: S-EPMC5006932 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature