1. Targeted SPP1 Inhibition of Tumor-Associated Myeloid Cells Effectively Decreases Tumor Sizes.
- Author
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Kartal B, Garris CS, Kim HS, Kohler RH, Carrothers J, Halabi EA, Iwamoto Y, Goubet AG, Xie Y, Wirapati P, Pittet MJ, and Weissleder R
- Subjects
- Animals, Mice, Disease Models, Animal, Osteopontin metabolism, Osteopontin genetics, Myeloid Cells drug effects, Cell Line, Tumor, Mice, Inbred C57BL, Humans, Tumor-Associated Macrophages drug effects, Tumor-Associated Macrophages metabolism, Tumor-Associated Macrophages immunology
- Abstract
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., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)- Published
- 2025
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