The tumor-targeted CD40 agonist CEA-CD40 promotes T cell priming via a dual mode of action by increasing antigen delivery to dendritic cells and enhancing their activation

Sum, Eva; Rapp, Moritz; Dürr, Harald; Mazumdar, Alekhya; Romero, Pedro J; Trumpfheller, Christine; Umaña, Pablo

doi:10.1136/jitc-2021-003264

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Sum, E., Rapp, M., Dürr, H., Mazumdar, A., Romero, P. J., Trumpfheller, C., & Umaña, P. (2022). The tumor-targeted CD40 agonist CEA-CD40 promotes T cell priming via a dual mode of action by increasing antigen delivery to dendritic cells and enhancing their activation. Journal for ImmunoTherapy of Cancer, 10(3), e003264. https://doi.org/10.1136/jitc-2021-003264

Abstract

Tumor-targeted CD40 agonism represents an attractive strategy for cancer immunotherapy (CIT) as it promotes dendritic cell (DC) activation and concomitant tumor-specific T cell priming without causing systemic side effects. We developed the bispecific CD40 agonistic antibody CEA-CD40, which triggers CD40 stimulation exclusively in the presence of carcinoembryonic antigen (CEA), a glycoprotein specifically expressed on tumor cells. In this study, we demonstrate that CEA-CD40 can enable potent in vitro DC activation and consecutive T ce