Children's Center for Cancer and Blood Diseases, Division of Hematology, Oncology, and Blood and Marrow Transplantation, Children's Hospital Los Angeles, The Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA; and.
Blood. 2014 Apr 17;123(16):2470-7. doi: 10.1182/blood-2014-01-492256. Epub 2014 Feb 27.
Unconjugated monoclonal antibodies that target hematopoietic differentiation antigens have been developed to treat hematologic malignancies. Although some of these have activity against chronic lymphocytic leukemia and hairy cell leukemia, in general, monoclonal antibodies have limited efficacy as single agents in the treatment of leukemia. To increase their potency, the binding domains of monoclonal antibodies can be attached to protein toxins. Such compounds, termed immunotoxins, are delivered to the interior of leukemia cells based on antibody specificity for cell surface target antigens. Recombinant immunotoxins have been shown to be highly cytotoxic to leukemic blasts in vitro, in xenograft model systems, and in early-phase clinical trials in humans. These agents will likely play an increasing role in the treatment of leukemia.
已经开发出针对造血分化抗原的未结合单克隆抗体来治疗血液系统恶性肿瘤。尽管其中一些对慢性淋巴细胞白血病和毛细胞白血病有活性,但总的来说,单克隆抗体作为单一药物在治疗白血病方面的疗效有限。为了提高它们的效力,可以将单克隆抗体的结合域连接到蛋白毒素上。此类化合物称为免疫毒素,基于抗体对细胞表面靶抗原的特异性递送至白血病细胞内部。重组免疫毒素已被证明在体外、异种移植模型系统和人类早期临床试验中对白血病细胞有高度细胞毒性。这些药物可能在白血病治疗中发挥越来越重要的作用。