Stimulation of Natural Killer Cell-Mediated Tumor Immunity by an IL15/TGFβ-Neutralizing Fusion Protein.

ABSTRACT: The clinical efficacy of immune cytokines used for cancer therapy is hampered by elements of the immunosuppressive tumor microenvironment such as TGFβ. Here we demonstrate that FIST15, a recombinant chimeric protein composed of the T-cell-stimulatory cytokine IL15, the sushi domain of IL15Rα and a TGFβ ligand trap, can overcome immunosuppressive TGFβ to effectively stimulate the proliferation and activation of natural killer (NK) and CD8⁺ T cells with potent antitumor properties. FIST15-treated NK and CD8⁺ T cells produced more IFNγ and TNFα compared with treatment with IL15 and a commercially available TGFβ receptor-Fc fusion protein (sTβRII) in the presence of TGFβ. Murine B16 melanoma cells, which overproduce TGFβ, were lysed by FIST15-treated NK cells in vitro at

SUBMITTER: Ng S 

PROVIDER: S-EPMC5050108 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature