Combination of rituximab with blinatumomab (MT103/MEDI-538), a T cell-engaging CD19-/CD3-bispecific antibody, for highly efficient lysis of human B lymphoma cells

被引：55
作者：
d'Argouges, Sandrine [1 ,2 ]
Wissing, Sandra [1 ,2 ]
Brandl, Christian [1 ,2 ]
Prang, Nadja [1 ,2 ]
Lutterbuese, Ralf [1 ,2 ]
Kozhich, Alex
Suzich, JoAnn [3 ]
Locher, Mathias [1 ,2 ]
Kiener, Peter [3 ]
Kufer, Peter [1 ,2 ]
Hofmeister, Robert [1 ,2 ]
Baeuerle, Patrick A. [1 ,2 ]
Bargou, Ralf C. [4 ]
机构：
[1] Micromet AG, D-81477 Munich, Germany
[2] Micromet Inc, Bethesda, MD 20817 USA
[3] MedImmune, Gaithersburg, MD 20878 USA
[4] Univ Klinikum Wurzburg, Med Klin & Poliklin 2, D-97070 Wurzburg, Germany
来源：
LEUKEMIA RESEARCH | 2009年 / 33卷 / 03期
关键词：
Rituximab; Blinatumomab; Combination; Antibody therapy; Natural killer cells; T cells; SINGLE-CHAIN ANTIBODY; ANTI-CD20; MONOCLONAL-ANTIBODY; CHRONIC LYMPHOCYTIC-LEUKEMIA; IN-VIVO; FOLLICULAR LYMPHOMA; CONSTRUCT; APOPTOSIS; CD20; CYTOTOXICITY; INHIBITION;
D O I：
10.1016/j.leukres.2008.08.025
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
We have compared the cytotoxic activity of rituximab with that of blinatumomab (MT103/MEDI-538), a single-chain CD19-/CD3-bispecific antibody engaging human T cells. Blinatumomab consistently led to a higher degree of lysis of human lymphoma lines than rituximab, and was active at much lower concentration. The cytotoxicity mediated by blinatumomab and rituximab both caused a potent activation of pro-caspases 3 and 7 in target cells, a key event in induction of granzyme-mediated apoptotic cell death. Combination of rituximab with blinatumomab was found to greatly enhance the activity of rituximab, in particular at low effector-to-target cell ratios and at low antibody concentration. (c) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码：465 / 473
页数：9
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