标题: 使用T细胞介导的双亲和重靶向平台靶向CD123在淋巴细胞白血病中的研究 [打印本页] 作者: icartab 时间: 2016-1-10 09:52 标题: 使用T细胞介导的双亲和重靶向平台靶向CD123在淋巴细胞白血病中的研究 Targeting CD123 in acute myeloid leukemia using a T-cell–directed dual-affinity retargeting platform
T-cell–directed killing of tumor cells using bispecific antibodies is a promising approach for the treatment of hematologic malignancies. Here we describe our preclinical work with a dual-affinity retargeting (DART) molecule generated from antibodies to CD3 and CD123, designed to redirect T cells against acute myeloid leukemia blasts. The CD3×CD123 DART (also referred to as MGD006/S80880) consists of 2 independent polypeptides, each composed of the VH of 1 antibody in tandem with the VL of the other antibody. The target antigen CD123 (interleukin 3RA) is highly and differentially expressed in acute myeloid leukemia (AML) blasts compared with normal hematopoietic stem and progenitor cells. In this study we demonstrate that the CD3×CD123 DART binds to both human CD3 and CD123 to mediate target-effector cell association, T-cell activation, proliferation, and receptor diversification. The CD3×CD123 DART also induces a dose-dependent killing of AML cell lines and primary AML blasts in vitro and in vivo. These results provide the basis for testing the CD3×CD123 DART in the treatment of patients with CD123+ AML.