A bispecific diabody that mediates natural killer cell cytotoxicity against xenotransplantated human Hodgkin's tumors
A bispecific diabody that mediates natural killer cell cytotoxicity against xenotransplantated human Hodgkin's tumors
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DOI：
10.1182/blood.v94.8.2562.420k20_2562_2568
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发表时间：
1999-10-15
期刊：
影响因子：
20.3
通讯作者：
Little, M
中科院分区：
文献类型：
--
作者：
Arndt, MAE;Krauss, J;Little, M
CD16/CD30双特异性单克隆抗体可诱导化疗和放疗难治性霍奇金病的缓解。然而，人类抗小鼠免疫球蛋白抗体和过敏反应的发展阻碍了抗体的重复应用。此外，生产和净化足够数量的材料的问题限制了这种新型治疗方法的临床实用性。为了克服这些障碍，我们在糖尿病体中构建了一种双特异性抗体，该抗体仅利用CD16/CD30杂交杂交瘤的可变结构域，该糖尿病体在体外激活和靶向自然杀伤细胞的能力方面优于亲本CD16/CD30双特异性抗体。将其施用于携带异种移植霍奇金淋巴瘤的小鼠后，肿瘤生长明显消退，从而首次证明了机体在体内进行免疫募集的能力。CD16/CD30抗体是一种新型试剂，可大大促进难治性霍奇金淋巴瘤患者的免疫治疗。(C) 1999年由美国血液病学会出版。
CD16/CD30 bispecific monoclonal antibodies can induce remissions of Hodgkin's disease refractory to chemo- and radiotherapy. However, the development of human anti-mouse immunoglobulin antibodies and allergic reactions precludes repeated applications of the antibody. Moreover, problems of producing and purifying sufficient amounts of material limit the clinical practicability of this novel treatment approach. To overcome these obstacles, we have constructed a bispecific antibody in a diabody form that only employs the variable domains of the CD16/CD30 hybrid hybridoma, The diabody compared favorably with the parent CD16/CD30 bispecific antibody in its ability to activate and target natural killer cells in vitro. Its administration to mice bearing xenografted Hodgkin's lymphoma resulted in a marked regression of tumor growth, thus proving for the first time the capability of a diabody for immune recruitment in vivo. The CD16/CD30 diabody is a novel reagent that should considerably facilitate the immunotherapy of patients with refractory Hodgkin's lymphoma. (C) 1999 by The American Society of Hematology.