American Association for Cancer Research (AACR)
Cancer immunology research
,  volume 13 ,  issue 5 ,  pages OF1-OF19

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

Vicky A Appleman 1, 2
, 
Atsushi Matsuda 2, 3
, 
Michelle L. Ganno 2, 4
, 
Dong Mei Zhang 2, 5
, 
Emily Rosentrater 1, 2
, 
Angel E. Maldonado Lopez 1, 2
, 
Angelo Porciuncula 6, 7
, 
Tiquella Hatten 1, 2
, 
Camilla L. Christensen 2, 8
, 
Samantha A. Merrigan 1, 9
, 
Hong Myung Lee 1, 10
, 
Min Young Lee 1, 11
, 
Charlotte I. Wang 12, 13
, 
Linlin Dong 1, 14
, 
Jian Huang 15, 16
, 
Natasha Iartchouk 17, 18
, 
Jianing Wang 19, 20
, 
He Xu 1, 10
, 
Tomoki Yoneyama 1, 21
, 
Konstantin Piatkov 1, 14
, 
Satyajeet Haridas 15, 22
, 
Carole E Harbison 23, 24
, 
Richard C Gregory 23, 25
, 
Alexander Parent 15, 26
, 
Neil Lineberry 27, 28
, 
Chris Arendt 11, 15
, 
Kurt A. Schalper 6, 7
, 
Adnan O Abu Yousif 2, 12
1
 
Takeda Development Center Americas, Inc., Lexington, MA, United States | 
2
 
1Oncology Drug Discovery Unit, Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts. | 
3
 
4
 
Takeda (United States), Cambridge, MA, United States | 
5
 
Takeda Development Center Americas, Inc., Lexington, United States | 
6
 
7
 
8
 
9
 
3Translational Sciences, Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts. | 
10
 
4Drug Discovery Science, Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts. | 
11
 
5Oncology Cell Therapy and Therapeutic Area Unit, Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts. | 
12
 
Takeda Development Center Americas, Inc., Lexington, Massachusetts, United States | 
13
 
6Clinical Science, Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts. | 
14
 
7Drug Metabolism and Pharmacokinetics, Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts. | 
15
 
Takeda Development Center Americas, Inc. (TDCA), Lexington, MA, United States | 
16
 
8Global Biologics, Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts. | 
17
 
18
 
9OTAU/PTM, Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts. | 
19
 
Ambrx, a Johnson and Johnson Company, San Diego, CA, United States | 
20
 
10Ambrx, San Diego, California. | 
21
 
11Quantitative Solutions, Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts. | 
22
 
12R&D excellence, ZS Associates, Boston, Massachusetts. | 
23
 
Takeda Development Center Americas, Inc., Cambridge, MA, United States | 
24
 
13DSRE, Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts. | 
25
 
14Precision and Translational Medicine, Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts. | 
26
 
15OTAU, Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts. | 
27
 
Takeda, Lexington, MA, United States | 
28
 
16Department of Oncology, Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts. | 
Publication type: Journal Article
Publication date: 2025-02-07
American Association for Cancer Research (AACR)
scimago Q1
wos Q1
SJR: 3.630
CiteScore: 12.8
Impact factor: 8.2
ISSN: 23266066, 23266074
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.

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Appleman V. A. et al. Selective STING Activation in Intratumoral Myeloid Cells via CCR2-Directed Antibody Drug Conjugate TAK-500 // Cancer immunology research. 2025. Vol. 13. No. 5. p. OF1-OF19.
GOST all authors (up to 50) Copy
Appleman V. A. et al. Selective STING Activation in Intratumoral Myeloid Cells via CCR2-Directed Antibody Drug Conjugate TAK-500 // Cancer immunology research. 2025. Vol. 13. No. 5. p. OF1-OF19.
RIS |
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RIS Copy
TY - JOUR
DO - 10.1158/2326-6066.cir-24-0103
UR - https://aacrjournals.org/cancerimmunolres/article/doi/10.1158/2326-6066.CIR-24-0103/751673/Selective-STING-Activation-in-Intratumoral-Myeloid
TI - Selective STING Activation in Intratumoral Myeloid Cells via CCR2-Directed Antibody Drug Conjugate TAK-500
T2 - Cancer immunology research
AU - Appleman, Vicky A
AU - Matsuda, Atsushi
AU - Ganno, Michelle L.
AU - Zhang, Dong Mei
AU - Rosentrater, Emily
AU - Maldonado Lopez, Angel E.
AU - Porciuncula, Angelo
AU - Hatten, Tiquella
AU - Christensen, Camilla L.
AU - Merrigan, Samantha A.
AU - Lee, Hong Myung
AU - Lee, Min Young
AU - Wang, Charlotte I.
AU - Dong, Linlin
AU - Huang, Jian
AU - Iartchouk, Natasha
AU - Wang, Jianing
AU - Xu, He
AU - Yoneyama, Tomoki
AU - Piatkov, Konstantin
AU - Haridas, Satyajeet
AU - Harbison, Carole E
AU - Gregory, Richard C
AU - Parent, Alexander
AU - Lineberry, Neil
AU - Arendt, Chris
AU - Schalper, Kurt A.
AU - Abu Yousif, Adnan O
PY - 2025
DA - 2025/02/07
PB - American Association for Cancer Research (AACR)
SP - OF1-OF19
IS - 5
VL - 13
SN - 2326-6066
SN - 2326-6074
ER -
BibTex |
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BibTex (up to 50 authors) Copy
@article{2025_Appleman,
author = {Vicky A Appleman and Atsushi Matsuda and Michelle L. Ganno and Dong Mei Zhang and Emily Rosentrater and Angel E. Maldonado Lopez and Angelo Porciuncula and Tiquella Hatten and Camilla L. Christensen and Samantha A. Merrigan and Hong Myung Lee and Min Young Lee and Charlotte I. Wang and Linlin Dong and Jian Huang and Natasha Iartchouk and Jianing Wang and He Xu and Tomoki Yoneyama and Konstantin Piatkov and Satyajeet Haridas and Carole E Harbison and Richard C Gregory and Alexander Parent and Neil Lineberry and Chris Arendt and Kurt A. Schalper and Adnan O Abu Yousif and others},
title = {Selective STING Activation in Intratumoral Myeloid Cells via CCR2-Directed Antibody Drug Conjugate TAK-500},
journal = {Cancer immunology research},
year = {2025},
volume = {13},
publisher = {American Association for Cancer Research (AACR)},
month = {feb},
url = {https://aacrjournals.org/cancerimmunolres/article/doi/10.1158/2326-6066.CIR-24-0103/751673/Selective-STING-Activation-in-Intratumoral-Myeloid},
number = {5},
pages = {OF1--OF19},
doi = {10.1158/2326-6066.cir-24-0103}
}
MLA
Cite this
MLA Copy
Appleman, Vicky A., et al. “Selective STING Activation in Intratumoral Myeloid Cells via CCR2-Directed Antibody Drug Conjugate TAK-500.” Cancer immunology research, vol. 13, no. 5, Feb. 2025, pp. OF1-OF19. https://aacrjournals.org/cancerimmunolres/article/doi/10.1158/2326-6066.CIR-24-0103/751673/Selective-STING-Activation-in-Intratumoral-Myeloid.