IL-15 synergizes with CD40 agonist antibodies to induce durable immunity against bladder cancer.

ABSTRACT: CD40 is a central co-stimulatory receptor implicated in the development of productive anti-tumor immune responses across multiple cancers, including bladder cancer. Despite strong preclinical rationale, systemic administration of therapeutic agonistic antibodies targeting the CD40 pathway have demonstrated dose limiting toxicities with minimal clinical activity to date, emphasizing an important need for optimized CD40-targeted approaches, including rational combination therapy strategies. Here, we describe an important role for the endogenous IL-15 pathway in contributing to the therapeutic activity of CD40 agonism in orthotopic bladder tumors, with upregulation of trans-presented IL-15/IL-15Rα surface complexes, particularly by cross-presenting cDC1s, and associated enrichment of activate

SUBMITTER: Wong JL 

PROVIDER: S-EPMC9915460 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature