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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1518787

Maplirpacept: A CD47 Decoy Receptor with Minimal Red Blood Cell Binding and Robust Anti-Tumor Efficacy

Provisionally accepted
Mithunah Krishnamoorthy Mithunah Krishnamoorthy 1,2*Ruth Seelige Ruth Seelige 1Christopher R Brown Christopher R Brown 1Nancy Chau Nancy Chau 1Natasja Nielsen Viller Natasja Nielsen Viller 2Lisa Johnson Lisa Johnson 2Emma Linderoth Emma Linderoth 2Jean C Y Wang Jean C Y Wang 3,4Christopher Dillon Christopher Dillon 1Keith Abayasiriwardana Keith Abayasiriwardana 1Clare Lees Clare Lees 1Mark Wong Mark Wong 2Megan M Kaneda Megan M Kaneda 1Robert A Uger Robert A Uger 2Gloria Lin Gloria Lin 1,2
  • 1 Pfizer, New York, United States
  • 2 Trillium Therapeutics (Canada), Toronto, Ontario, Canada
  • 3 Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario, Canada
  • 4 University of Toronto, Toronto, Ontario, Canada

The final, formatted version of the article will be published soon.

    CD47 is highly expressed on cancer cells and triggers an anti-phagocytic "don't eat me" signal when bound by the inhibitory signal regulatory protein α (SIRPα) 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 SIRPα fused to an IgG4 Fc region and designed to limit binding to RBCs. In the current study, we demonstrate that maplirpacept has limited binding to RBCs while driving enhanced macrophage-mediated phagocytosis of hematological tumor cells in vitro 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. Collectively, these preclinical results establish maplirpacept as an effective CD47 blocker that mitigates the potential for anemia in patients.

    Keywords: cd47, Phagocytosis, red blood cells, Hematological malignances, SIRP alpha

    Received: 28 Oct 2024; Accepted: 05 Feb 2025.

    Copyright: © 2025 Krishnamoorthy, Seelige, Brown, Chau, Nielsen Viller, Johnson, Linderoth, Wang, Dillon, Abayasiriwardana, Lees, Wong, Kaneda, Uger and Lin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Mithunah Krishnamoorthy, Pfizer, New York, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.