Targeted SPP1 Inhibition of Tumor‐Associated Myeloid Cells Effectively Decreases Tumor Sizes
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...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202410360 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832582743630807040 |
|---|---|
| author | Benan Kartal Christopher S. Garris Hyung Shik Kim Rainer H. Kohler Jasmine Carrothers Elias A. Halabi Yoshiko Iwamoto Anne‐Gaëlle Goubet Yuxuan Xie Pratyaksha Wirapati Mikaël J. Pittet Ralph Weissleder |
| author_facet | Benan Kartal Christopher S. Garris Hyung Shik Kim Rainer H. Kohler Jasmine Carrothers Elias A. Halabi Yoshiko Iwamoto Anne‐Gaëlle Goubet Yuxuan Xie Pratyaksha Wirapati Mikaël J. Pittet Ralph Weissleder |
| author_sort | Benan Kartal |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-463f2aee13d64a50ab0533bab46ace65 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-463f2aee13d64a50ab0533bab46ace652025-01-29T09:50:19ZengWileyAdvanced Science2198-38442025-01-01124n/an/a10.1002/advs.202410360Targeted SPP1 Inhibition of Tumor‐Associated Myeloid Cells Effectively Decreases Tumor SizesBenan Kartal0Christopher S. Garris1Hyung Shik Kim2Rainer H. Kohler3Jasmine Carrothers4Elias A. Halabi5Yoshiko Iwamoto6Anne‐Gaëlle Goubet7Yuxuan Xie8Pratyaksha Wirapati9Mikaël J. Pittet10Ralph Weissleder11Center for Systems Biology Massachusetts General Hospital 185 Cambridge St, CPZN 5206 Boston MA 02114 USACenter for Systems Biology Massachusetts General Hospital 185 Cambridge St, CPZN 5206 Boston MA 02114 USACenter for Systems Biology Massachusetts General Hospital 185 Cambridge St, CPZN 5206 Boston MA 02114 USACenter for Systems Biology Massachusetts General Hospital 185 Cambridge St, CPZN 5206 Boston MA 02114 USACenter for Systems Biology Massachusetts General Hospital 185 Cambridge St, CPZN 5206 Boston MA 02114 USACenter for Systems Biology Massachusetts General Hospital 185 Cambridge St, CPZN 5206 Boston MA 02114 USACenter for Systems Biology Massachusetts General Hospital 185 Cambridge St, CPZN 5206 Boston MA 02114 USADepartment of Pathology and Immunology University of Geneva Geneva 1211 SwitzerlandDepartment of Pathology and Immunology University of Geneva Geneva 1211 SwitzerlandDepartment of Pathology and Immunology University of Geneva Geneva 1211 SwitzerlandDepartment of Pathology and Immunology University of Geneva Geneva 1211 SwitzerlandCenter for Systems Biology Massachusetts General Hospital 185 Cambridge St, CPZN 5206 Boston MA 02114 USAAbstract 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.https://doi.org/10.1002/advs.202410360cancermacrophagenanoparticlesSPP1 |
| spellingShingle | Benan Kartal Christopher S. Garris Hyung Shik Kim Rainer H. Kohler Jasmine Carrothers Elias A. Halabi Yoshiko Iwamoto Anne‐Gaëlle Goubet Yuxuan Xie Pratyaksha Wirapati Mikaël J. Pittet Ralph Weissleder Targeted SPP1 Inhibition of Tumor‐Associated Myeloid Cells Effectively Decreases Tumor Sizes Advanced Science cancer macrophage nanoparticles SPP1 |
| title | Targeted SPP1 Inhibition of Tumor‐Associated Myeloid Cells Effectively Decreases Tumor Sizes |
| title_full | Targeted SPP1 Inhibition of Tumor‐Associated Myeloid Cells Effectively Decreases Tumor Sizes |
| title_fullStr | Targeted SPP1 Inhibition of Tumor‐Associated Myeloid Cells Effectively Decreases Tumor Sizes |
| title_full_unstemmed | Targeted SPP1 Inhibition of Tumor‐Associated Myeloid Cells Effectively Decreases Tumor Sizes |
| title_short | Targeted SPP1 Inhibition of Tumor‐Associated Myeloid Cells Effectively Decreases Tumor Sizes |
| title_sort | targeted spp1 inhibition of tumor associated myeloid cells effectively decreases tumor sizes |
| topic | cancer macrophage nanoparticles SPP1 |
| url | https://doi.org/10.1002/advs.202410360 |
| work_keys_str_mv | AT benankartal targetedspp1inhibitionoftumorassociatedmyeloidcellseffectivelydecreasestumorsizes AT christophersgarris targetedspp1inhibitionoftumorassociatedmyeloidcellseffectivelydecreasestumorsizes AT hyungshikkim targetedspp1inhibitionoftumorassociatedmyeloidcellseffectivelydecreasestumorsizes AT rainerhkohler targetedspp1inhibitionoftumorassociatedmyeloidcellseffectivelydecreasestumorsizes AT jasminecarrothers targetedspp1inhibitionoftumorassociatedmyeloidcellseffectivelydecreasestumorsizes AT eliasahalabi targetedspp1inhibitionoftumorassociatedmyeloidcellseffectivelydecreasestumorsizes AT yoshikoiwamoto targetedspp1inhibitionoftumorassociatedmyeloidcellseffectivelydecreasestumorsizes AT annegaellegoubet targetedspp1inhibitionoftumorassociatedmyeloidcellseffectivelydecreasestumorsizes AT yuxuanxie targetedspp1inhibitionoftumorassociatedmyeloidcellseffectivelydecreasestumorsizes AT pratyakshawirapati targetedspp1inhibitionoftumorassociatedmyeloidcellseffectivelydecreasestumorsizes AT mikaeljpittet targetedspp1inhibitionoftumorassociatedmyeloidcellseffectivelydecreasestumorsizes AT ralphweissleder targetedspp1inhibitionoftumorassociatedmyeloidcellseffectivelydecreasestumorsizes |