Data from Selective STING Activation in Intratumoral Myeloid Cells via CCR2-Directed Antibody–Drug Conjugate TAK-500
Year: 2025
Type: other
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 in vitro and murine tumor models. Spatially resolved analysis of CCR2 and immune cell markers in the tumor microenvironment of >1,000 primary human tumors showed that the CCR2 protein was predominantly expressed in intratumoral myeloid cells. Collectively, these data highlight the clinical potential of delivering a STING agonist to CCR2+ cells.
Authors: Vicky A. Appleman, Atsushi Matsuda, Michelle L. Ganno, Dong Mei Zhang, Emily Rosentrater, Angel E. Maldonado Lopez, Angelo Porciuncula, Tiquella Hatten, Camilla L. Christensen, Samantha A. Merrigan, Hong Myung Lee, Min Young Lee, Charlotte I. Wang, Linlin Dong, Jian Huang, Natasha Iartchouk, Jianing Wang, He Xu, Tomoki Yoneyama, Konstantin I. Piatkov, Satyajeet Haridas, Carole E. Harbison, Richard C. Gregory, Alexander Parent, Neil Lineberry, Chris Arendt, Kurt A. Schalper, Adnan O. Abu-Yousif
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4410047719