Discovery and Characterization of a First-in-Class LIV1-TLR7/8 Immunomodulatory Conjugate with Robust Myeloid Activation and Antitumor Activity.

ABSTRACT: Herein, we describe the discovery of a novel immunostimulatory drug conjugate (IMC) that employs TLR7/8 agonists conjugated to a tumor-targeting LIV1 antibody. Targeting TLR7/8 agonists to LIV1-expressing tumors enables localized delivery, thereby minimizing systemic toxicity while promoting inflammation and T cell recruitment within the tumor microenvironment (TME) for enhanced antitumor efficacy. Dual activation of TLR7 and TLR8 within the TME facilitates the recruitment of diverse immune cells and induces a broad spectrum of pro-inflammatory cytokines, effectively reshaping the immunosuppressive TME by upregulating costimulatory molecules. The mechanism of action of the IMC involves tumor recognition via surface antigens and Fcγ-mediated phagocytosis, followed by activation of myeloid c

SUBMITTER: Yamazoe S 

PROVIDER: S-EPMC12169649 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature