biostudies-literatureUnknown13(5)Appleman VATakeda Development Center Americas, Inc. (TDCA), Lexington, MAThe 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 Cancer immunology research661-679https://www.ebi.ac.uk/biostudies/studies/S-EPMC12046323biostudies-literatureSelective STING Activation in Intratumoral Myeloid Cells via CCR2-Directed Antibody-Drug Conjugate TAK-500.PMC12046323Christensen CLWang CIHuang JPorciuncula ADong LHaridas SAbu-Yousif AOLineberry NGanno MLWang JLee MYParent ALee HMIartchouk NMatsuda ARosentrater EHatten TArendt CZhang DMAppleman VAPiatkov KIXu HGregory RCYoneyama TMaldonado Lopez AESchalper KAMerrigan SAHarbison CEfalseSelective STING Activation in Intratumoral Myeloid Cells via CCR2-Directed Antibody-Drug Conjugate TAK-500.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 2025-01-01T00:00:00Z2025 May2025-07-08T03:10:33.775Z2025-07-08T03:10:33.775ZS-EPMC120463233991839510.1158/2326-6066.CIR-24-0103