Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma.
Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma.
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DOI：
10.1016/j.cell.2010.07.044
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发表时间：
2010-09-03
期刊：
影响因子：
64.5
通讯作者：
Majeti R
中科院分区：
文献类型：
--
作者：
Chao MP;Alizadeh AA;Tang C;Myklebust JH;Varghese B;Gill S;Jan M;Cha AC;Chan CK;Tan BT;Park CY;Zhao F;Kohrt HE;Malumbres R;Briones J;Gascoyne RD;Lossos IS;Levy R;Weissman IL;Majeti R
单抗是几种癌症的标准疗法，包括用于B细胞非霍奇金淋巴瘤(NHL)的抗CD20抗体美妥昔单抗。利妥昔单抗和其他抗体不能治愈，必须与细胞毒性化疗联合使用才能临床受益。在这里，我们报告了仅用单抗疗法根除人类非霍奇金淋巴瘤，联合利妥昔单抗和封闭的抗CD47抗体。我们鉴定了CD47在人类NHL细胞上的高表达，并确定在多种NHL亚型中，CD47的高表达独立地预测不良的临床结果。阻断抗CD47抗体优先促进NHL细胞的吞噬，并与利妥昔单抗协同作用。用抗CD47抗体治疗移植人非霍奇金淋巴瘤的小鼠可以减少淋巴瘤负担，提高存活率，而联合利妥昔单抗治疗可以消除淋巴瘤并治愈。这些抗体通过一种结合Fc受体(FCR)依赖和FCR非依赖的吞噬刺激的机制协同作用，这可能适用于许多其他癌症。
Monoclonal antibodies are standard therapeutics for several cancers including the anti-CD20 antibody rituximab for B cell non-Hodgkin lymphoma (NHL). Rituximab and other antibodies are not curative, and must be combined with cytotoxic chemotherapy for clinical benefit. Here we report the eradication of human NHL solely with a monoclonal antibody therapy combining rituximab with a blocking anti-CD47 antibody. We identified increased expression of CD47 on human NHL cells, and determined that higher CD47 expression independently predicted adverse clinical outcomes in multiple NHL subtypes. Blocking anti-CD47 antibodies preferentially enabled phagocytosis of NHL cells and synergized with rituximab. Treatment of human NHL-engrafted mice with anti-CD47 antibody reduced lymphoma burden and improved survival, while combination treatment with rituximab led to elimination of lymphoma and cure. These antibodies synergized through a mechanism combining Fc receptor (FcR)-dependent and FcR-independent stimulation of phagocytosis that might be applicable to many other cancers.
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DOI：
10.1016/j.bbrc.2004.01.128
发表时间：
2004-03-19
影响因子：
3.1
作者：
Kikuchi, Y;Uno, S;Tsuchiya, M
通讯作者：
Tsuchiya, M
CD47是人类急性髓样白血病干细胞的不良预后因素和治疗抗体靶标。
影响因子：
64.5
作者：
Majeti R;Chao MP;Alizadeh AA;Pang WW;Jaiswal S;Gibbs KD Jr;van Rooijen N;Weissman IL
通讯作者：
Weissman IL
DOI：
10.1073/pnas.0906549106
发表时间：
2009-08-18
影响因子：
11.1
作者：
Chan, Keith Syson;Espinosa, Inigo;Weissman, Irving L.
通讯作者：
Weissman, Irving L.
影响因子：
3.6
作者：
Glennie, Martin J.;French, Ruth R.;Taylor, Ronald P.
通讯作者：
Taylor, Ronald P.
影响因子：
64.8
作者：
Alizadeh, AA;Eisen, MB;Staudt, LM
通讯作者：
Staudt, LM