期刊
LEUKEMIA
卷 26, 期 12, 页码 2538-2545出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/leu.2012.141
关键词
multiple myeloma; myeloma-initiating cells; CD47; xenotransplantation; therapeutic antibody
资金
- Irvington Institute Fellowship Program of the Cancer Research Institute
- Irvington Institute for Immunological Research
- Dana Foundation
- Multiple Myeloma Research Foundation [43710]
- Leukemia Lymphoma Society
- Ludwig Institute
Multiple myeloma is a plasma cell neoplasm residing in bone marrow. Despite advances in myeloma therapies, novel therapies are required to improve patient outcomes. CD47 is highly expressed on myeloma cells and a potential therapeutic candidate for myeloma therapies. Flow cytometric analysis of patient bone marrow cells revealed that myeloma cells overexpress CD47 when compared with non-myeloma cells in 73% of patients (27/37). CD47 expression protects cells from phagocytosis by transmitting an inhibitory signal to macrophages. Here we show that blocking CD47 with an anti-CD47 monoclonal antibody increased phagocytosis of myeloma cells in vitro. In xenotransplantation models, anti-CD47 antibodies inhibited the growth of RPMI 8226 myeloma cells and led to tumor regression (42/57 mice), implicating the eradication of myeloma-initiating cells. Moreover, anti-CD47 antibodies retarded the growth of patient myeloma cells and alleviated bone resorption in human bone-bearing mice. Irradiation of mice before myeloma cell xenotransplantation abolished the therapeutic efficacy of anti-CD47 antibodies delivered 2 weeks after radiation, and coincided with a reduction of myelomonocytic cells in spleen, bone marrow and liver. These results are consistent with the hypothesis that anti-CD47 blocking antibodies inhibit myeloma growth, in part, by increasing phagocytosis of myeloma cells. Leukemia (2012) 26, 2538-2545; doi:10.1038/leu.2012.141
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