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- W4380186088 abstract "JMML is a highly aggressive childhood leukemia. The only curative treatment is allogeneic hematopoietic stem cell transplantation (HSCT) but the risk of relapse is high, especially for PTPN11 mutated patients. JMML cells express various immune checkpoints that may mediate immune escape. Amongst others, we identified the ‘don’t eat me’ signal CD47 that prevents leukemia cell phagocytosis. We aim to understand the impact of CD47 on immune escape and to test how CD47 inhibition affects disease presentation and risk of relapse. We are using PTPN11-knockin mice, primary JMML cells and patient-derived xenograft mice (PDX). CD47 is highly expressed on human JMML and murine stem and myeloid splenic cells. Phagocytosis assays revealed that anti-CD47 could enhance phagocytosis of both, human and murine cells. Use of Magrolimab in PDX mice resulted in strong depletion of human JMML cells in the spleen and liver but only with mild depletion in the bone marrow. We will next establish a relapse JMML mouse model to test the effect of anti-CD47 treatment on relapse risk. Our studies will pave the way for future anti-CD47 antibody clinical trials." @default.
- W4380186088 created "2023-06-11" @default.
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- W4380186088 date "2023-05-01" @default.
- W4380186088 modified "2023-09-27" @default.
- W4380186088 title "Inhibition of the ”don’t eat me signal” CD47 to prevent relapse in juvenile myelomonocytic leukemia" @default.
- W4380186088 doi "https://doi.org/10.1055/s-0043-1768556" @default.
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