Reverse Translation Identifies the Synergistic Role of Immune Checkpoint Blockade and IL15 to Enhance Immunotherapy of Ovarian Cancer.

ABSTRACT: Immune checkpoint blockade (ICB) has changed the standard of care for many patients with cancer, yet no ICB is approved for ovarian cancer. We hypothesized that maintenance therapy with an IL15 "superagonist" (N-803) and ICB in combination could induce potent immune activation in ovarian cancer. Using flow cytometry, cytometry by time of flight analysis, and cytotoxicity assays, we analyzed patient samples from women with advanced epithelial ovarian cancer treated with N-803 for indications of PD-1/PD-L1 upregulation with this treatment. In addition, ICB and N-803 were evaluated in preclinical studies to determine the functional impact of combination therapy on natural killer (NK) cells in vitro and in vivo. We observed that N-803 stimulated initial NK-cell expansion in patient samples; ho

SUBMITTER: Felices M 

PROVIDER: S-EPMC10155036 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature