Sustained Intratumoral Administration of Agonist CD40 Antibody Overcomes Immunosuppressive Tumor Microenvironment in Pancreatic Cancer.

ABSTRACT: Agonist CD40 monoclonal antibodies (mAb) is a promising immunotherapeutic agent for cold-to-hot tumor immune microenvironment (TIME) conversion. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal cancer known as an immune desert, and therefore urgently needs more effective treatment. Conventional systemic treatment fails to effectively penetrate the characteristic dense tumor stroma. Here, it is shown that sustained low-dose intratumoral delivery of CD40 mAb via the nanofluidic drug-eluting seed (NDES) can modulate the TIME to reduce tumor burden in murine models. NDES achieves tumor reduction at a fourfold lower dosage than systemic treatment while avoiding treatment-related adverse events. Further, abscopal responses are shown where intratumoral treatment yields growth i

SUBMITTER: Liu HC 

PROVIDER: S-EPMC10037694 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature