Targeted SPP1 Inhibition of Tumor-Associated Myeloid Cells Effectively Decreases Tumor Sizes

被引：3

作者：

Kartal, Benan ^{[1
]}

Garris, Christopher S. ^{[1
]}

Kim, Hyung Shik ^{[1
]}

Kohler, Rainer H. ^{[1
]}

Carrothers, Jasmine ^{[1
]}

Halabi, Elias A. ^{[1
]}

Iwamoto, Yoshiko ^{[1
]}

Goubet, Anne-Gaelle ^{[2
,3
]}

Xie, Yuxuan ^{[2
,3
]}

Wirapati, Pratyaksha ^{[2
,3
]}

Pittet, Mikael J. ^{[2
,3
,4
]}

Weissleder, Ralph ^{[1
,5
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA

[2] Univ Geneva, Dept Pathol & Immunol, CH-1211 Geneva, Switzerland

[3] Swiss Canc Ctr Leman, AGORA Canc Res Ctr, CH-1011 Lausanne, Switzerland

[4] Ludwig Inst Canc Res, CH-1005 Lausanne, Switzerland

[5] Harvard Med Sch, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA

来源：

ADVANCED SCIENCE | 2025年 / 12卷 / 04期

基金：

瑞士国家科学基金会;

关键词：

cancer; macrophage; nanoparticles; SPP1; SINGLE-CELL; THERAPEUTIC TARGET; MACROPHAGES; OSTEOPONTIN; CANCER; EXPRESSION; POLARIZATION; FIBROBLASTS; GROWTH;

D O I：

10.1002/advs.202410360

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Secreted phosphosprotein 1 (SPP1)High tumor-associated macrophages (TAM) are abundant tumor myeloid cells that are immunosuppressive, pro-tumorigenic, and have a highly negative prognostic factor. Despite this, there is a lack of efficient TAM-specific therapeutics capable of reducing SPP1 expression. Here, on a phenotypic screen is reported to identify small molecule SPP1 modulators in macrophages. Several hits and incorporated them into a TAM-avid systemic nanoformulation are identified. It is shown that the lead compound (CANDI460) can down-regulate SPP1 in vitro and in vivo and lead to tumor remissions in different murine models. These findings are important as they offer a promising avenue for developing novel therapeutic strategies targeting TAM.

引用

页数：11

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