Therapeutic applications of a novel humanized monoclonal antibody targeting chemokine receptor CCR9 in pancreatic cancer.

ABSTRACT: The relative failure of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma (PDAC) despite having a dense, immunosuppressive tumor microenvironment highlights the need to target alternate/escape pathways. We have previously examined C-C chemokine receptor type 9 (CCR9) as a candidate immune checkpoint and developed a targeted, humanized monoclonal antibody (SRB2). Cytotoxicity of SRB2 was evaluated in vitro and in vivo. CCR9 expression on PDAC cells/tissues, immune components of patient-derived organoids (PDOs), and antibody-dependent cell-mediated cytotoxicity were examined. In PANC-1 and MIA PaCa-2 cell lines, we demonstrated highest CCR9 expression; however, no direct cytotoxic effect was observed with SRB2 treatment. In PANC-1 cells, NK cell-mediated cytotoxicity was promo

SUBMITTER: McDonald HG 

PROVIDER: S-EPMC12515709 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature