Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
Targeted SPP1 Inhibition of Tumor-Associated Myeloid Cells Effectively Decreases Tumor Sizes.
СтатьяНазвание и аннотация: Перевод в очереди
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Kartal Benan, Garris Christopher S, Kim Hyung Shik, Kohler Rainer H, Carrothers Jasmine, Halabi Elias A, Iwamoto Yoshiko, Goubet Anne-Gaëlle, Xie Yuxuan, Wirapati Pratyaksha, Pittet Mikaël J, Weissleder Ralph
Аннотация
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.