{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:59:08Z","timestamp":1790297948548,"version":"4.1.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>CD47 is highly expressed on cancer cells and triggers an anti-phagocytic \u201cdon\u2019t eat me\u201d signal when bound by the inhibitory signal regulatory protein \u03b1 (SIRP\u03b1) expressed on macrophages. While CD47 blockade can mitigate tumor growth, many CD47 blockers also bind to red blood cells (RBCs), leading to anemia. Maplirpacept (TTI-622, PF-07901801) is a CD47 blocking fusion protein consisting of a human SIRP\u03b1 fused to an IgG4 Fc region and designed to limit binding to RBCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To determine maplirpacept binding to RBCs and interference with blood tests, human blood samples were used. The ability of maplirpacept to promote macrophage-mediated phagocytosis of human tumor cells was assessed using both confocal microscopy and flow cytometry. <jats:italic>In vivo<\/jats:italic> antitumor efficacy as a monotherapy and in combination with other therapeutic agents was evaluated in xenograft models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the current study, we demonstrate that maplirpacept has limited binding to RBCs while driving enhanced macrophage-mediated phagocytosis of hematological tumor cells <jats:italic>in vitro<\/jats:italic> and reducing tumor burden in human xenograft models. Moreover, phagocytosis of neoplastic cells can be enhanced when maplirpacept is combined with other therapeutic agents, including antibodies or chemotherapeutic agents.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These preclinical results establish maplirpacept as an effective CD47 blocker that mitigates the potential for anemia in patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1518787","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T07:25:00Z","timestamp":1740554700000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Maplirpacept: a CD47 decoy receptor with minimal red blood cell binding and robust anti-tumor efficacy"],"prefix":"10.3389","volume":"16","author":[{"given":"Mithunah","family":"Krishnamoorthy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Seelige","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Chau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasja","family":"Nielsen Viller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa D. 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