A novel anti-PD-L1/IL-15 immunocytokine overcomes resistance to PD-L1 blockade and elicits potent antitumor immunity.

ABSTRACT: Despite the demonstrated immense potential of immune checkpoint inhibitors in various types of cancers, only a minority of patients respond to these therapies. Immunocytokines designed to deliver an immune-activating cytokine directly to the immunosuppressive tumor microenvironment (TME) and block the immune checkpoint simultaneously may provide a strategic advantage over the combination of two single agents. To increase the response rate to checkpoint blockade, in this study, we developed a novel immunocytokine (LH01) composed of the antibody against programmed death-ligand 1 (PD-L1) fused to interleukin (IL)-15 receptor alpha-sushi domain/IL-15 complex. We demonstrate that LH01 efficiently binds mouse or human PD-L1 and maintains IL-15 stimulatory activity. In syngeneic mouse models, LH0

SUBMITTER: Shi W 

PROVIDER: S-EPMC9840182 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature