Abstract 6083: A fully human agonistic antibody against a unique epitope on TREM1 demonstrates immune stimulatory activities both in vitro and in vivo

Abstract Triggering receptor expressed on myeloid cells-1 (TREM1) is a proinflammatory receptor that amplifies immune responses. TREM1 is expressed on neutrophils, subsets of monocytes and tissue macrophages, and suppressive myeloid populations in the tumor microenvironment (TME), including tumor-associated neutrophils, monocytes, and tumor-associated macrophages. Stimulation by TREM1-mediated inflammatory signaling may promote an immunostimulatory TME and inhibit tumor growth. We developed DX002, a fully human agonistic anti-TREM1 monoclonal antibody. DX002 binds to a unique epitope and has low internalization property. Deep mutational scanning (DMS) of the human TREM1 antigen was applied to map DX002 binding epitope and result showed that DX002 was a ligand-competitive agonist that mimic the function of ligand PGLYRP1 protein. In vitro, Plate-bound DX002 up-regulates the expression of costimulatory molecules on monocytes and induces the production of proinflammatory cytokines. Moreover, soluble DX002 also induces the production of proinflammatory cytokines in PBMCs. In vivo, DX002 exhibits significant tumor growth inhibition activity in MC38 syngeneic model in human TREM1 transgenic mice. Taken together, the TREM1 agonistic antibody DX002 is shown to be active both in vitro and in vivo. Citation Format: Lan Yang, Di Liu, Zhen Zhang, Yan Jiang, Qinghao Liu, Qian Shi. A fully human agonistic antibody against a unique epitope on TREM1 demonstrates immune stimulatory activities both in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6083.