Related Experiment Video
Updated: May 22, 2025
A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells
Published on: November 12, 2019
Maplirpacept: a CD47 decoy receptor with minimal red blood cell binding and robust anti-tumor efficacy
Mithunah Krishnamoorthy1,2, Ruth Seelige1, Christopher R Brown1
1Pfizer Oncology, Pfizer Inc., La Jolla, CA, United States.
Introduction:
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.
Methods:
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. In vivo antitumor efficacy as a monotherapy and in combination with other therapeutic agents was evaluated in xenograft models.
Results:
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.
Conclusion:
These preclinical results establish maplirpacept as an effective CD47 blocker that mitigates the potential for anemia in patients.
Insights
Maplirpacept is a novel CD47 blocker that effectively targets cancer cells by enhancing phagocytosis. Unlike other blockers, it shows limited binding to red blood cells, reducing the risk of anemia in patients.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- CD47 on cancer cells signals macrophages to inhibit phagocytosis via SIRPα.
- CD47 blockade is a promising cancer therapy but often causes anemia due to red blood cell binding.
- Maplirpacept is a fusion protein designed to block CD47 while minimizing red blood cell interaction.
Purpose of the Study:
- To evaluate maplirpacept's binding to red blood cells.
- To assess maplirpacept's efficacy in promoting phagocytosis of tumor cells.
- To determine the in vivo antitumor activity of maplirpacept.
Main Methods:
- Human blood samples were used to test maplirpacept binding to red blood cells.
- Confocal microscopy and flow cytometry assessed macrophage-mediated phagocytosis of tumor cells.
- Xenograft models were used to evaluate antitumor efficacy as monotherapy and in combination.
Main Results:
- Maplirpacept demonstrated limited binding to red blood cells.
- Enhanced macrophage-mediated phagocytosis of hematological tumor cells was observed in vitro.
- Reduced tumor burden was achieved in human xenograft models, with enhanced efficacy when combined with other agents.
Conclusions:
- Maplirpacept is an effective CD47 blocker with a reduced potential for causing anemia.
- Preclinical data support maplirpacept's therapeutic potential in treating cancer.
