Selective STING Activation in Intratumoral Myeloid Cells via CCR2-Directed Antibody-Drug Conjugate TAK-500.

ABSTRACT: The tumor microenvironment in solid tumors contains myeloid cells that modulate local immune activity. Stimulator of IFN gene (STING) signaling activation in these myeloid cells enhances local type-I IFN production, inducing an innate immune response that mobilizes adaptive immunity and reprograms immunosuppressive myeloid populations to drive antitumor immunity. In this study, we generated TAK-500, an immune cell-directed antibody-drug conjugate, to deliver a STING agonist to CCR2+ human cells and drive enhanced antitumor activity relative to nontargeted STING agonists. Preclinically, TAK-500 triggered dose-dependent innate immune activation in vitro. In addition, a murine TAK-500 immune cell-directed antibody-drug conjugate surrogate enhanced innate and adaptive immune responses both in

SUBMITTER: Appleman VA 

PROVIDER: S-EPMC12046323 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature