Administration of agonistic anti‐4–1 BB monoclonal antibody inhibits melanoma metastasis via IFN‐γ production

The purpose of this study was to analyze inhibitory effects of anti‐4–1 BBmonoclonal antibody on melanoma metastasis. The 4–1 BB (CD137) T cell molecule is amember of the TNF receptor family and its activation by either 4–1 BB ligand or antibody induces T cell activation and growth. In the present study, administration of anti‐4–1BB mAb induced inhibition of melanoma metastasis. Agonistic anti‐4–1 BB mAb induced not only CD8+4–1BB+ T cells but also CD8+IFN‐γ+ T cell population. In the presence of anti‐CD3 antibody, lymphocytes produced high levels of IFN‐γ and low levels of IL‐4 in anti‐4–1 BB mAb treated group. Exposure of melanoma cells to IFN‐γ induced expression of MHC‐I molecules. Thus, the increase in number of CD8+ T cells and enhanced MHC‐I expression on B16F10 cells by augmented IFN‐γ production in response to anti‐4–1 BB mAb may result in suppression of tumor growth and metastasis.