IGM-7354, an Immunocytokine with IL15 Fused to an Anti-PD-L1 IgM, Induces NK and CD8+ T cell-Mediated Cytotoxicity of PD-L1-Positive Tumor Cells.

ABSTRACT: IgM antibodies are preformed pentameric or hexameric molecules that can be engineered to generate high-affinity and high-avidity fully human antibody therapeutics. In this study, we report an immunocytokine, IGM-7354, which was designed to bind multiple PD-L1 receptors while trans-presenting a single IL15/IL15Rα complex on the joining chain to IL15Rβγ-expressing cytotoxic NK and CD8+ T cells. We evaluated the pharmacologic and antitumor properties of IGM-7354 in preclinical models. IGM-7354 induced potent proliferation of NK and CD8+ T cells, both in vitro using healthy human peripheral blood mononuclear cells and in vivo in humanized mice, through the IL15/IL15Rα complex. In a mixed-lymphocyte reaction assay with exhausted human T cells, IGM-7354 restored the secretion of IFNγ compared wi

SUBMITTER: Desbois M 

PROVIDER: S-EPMC12314523 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature