College of Medical, Henan University of Science and Technology, Luoyang, Henan, China.
The Second Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, China.
Biochem Biophys Res Commun. 2019 Feb 12;509(3):739-745. doi: 10.1016/j.bbrc.2018.12.175. Epub 2019 Jan 3.
T cell immunotherapies are promising options in leukemia, among which the CD19/CD3-bispecific T cell engager antibody blinatumomab (MT103) has shown high response rates at very low doses in patients with lymphoma. However, the high CD47 expression in human lymphoma cells has limited the curative effects of blinatumomab other antibodies. Here we report the combined use of blinatumomab with a CD47-blocking antibody. CD47 antibodies preferentially enabled phagocytosis of non-Hodgkin lymphoma cells by both human and murine macrophages. Treatment of human non-Hodgkin lymphoma cell-engrafted mice with CD47 antibody and blinatumomab separately inhibited lymphoma partially, while combination treatment led to persistent control of lymphoma. These antibodies enhanced the therapeutic efficacy through mechanisms combining both innate and adaptive immune responses by induction of phagocytosis and T cell cytotoxicity. The combination strategy in this study might be applicable to many other cancers.
T 细胞免疫疗法在白血病中是一种很有前途的选择，其中 CD19/CD3 双特异性 T 细胞衔接抗体blinatumomab（MT103）在淋巴瘤患者中以非常低的剂量显示出了很高的反应率。然而，人淋巴瘤细胞中高表达的 CD47 限制了 blinatumomab 等其他抗体的疗效。在这里，我们报告了将 blinatumomab 与 CD47 阻断抗体联合使用。CD47 抗体优先使人类和鼠类巨噬细胞吞噬非霍奇金淋巴瘤细胞。用 CD47 抗体和 blinatumomab 分别治疗人非霍奇金淋巴瘤细胞移植小鼠，部分抑制了淋巴瘤，而联合治疗则导致淋巴瘤持续得到控制。这些抗体通过诱导吞噬作用和 T 细胞细胞毒性，通过固有和适应性免疫反应的结合机制增强了治疗效果。本研究中的联合策略可能适用于许多其他癌症。
