Selective killing of malignant cells in a leukaemic rat bone marrow using an antibody–ricin conjugate
Selective killing of malignant cells in a leukaemic rat bone marrow using an antibody–ricin conjugate
复制标题
使用抗体-蓖麻毒素结合物选择性杀死白血病大鼠骨髓中的恶性细胞
DOI：
10.1038/297594a0
复制
发表时间：
1982
期刊：
影响因子：
64.8
通讯作者：
J. Forrester
中科院分区：
文献类型：
--
作者：
P. Thorpe;D. Mason;A. Brown;S. Simmonds;W. Ross;A. Cumber;J. Forrester
移植物抗宿主病和骨髓移植排斥反应是全身放疗、大剂量化疗和骨髓移植治疗白血病的两个主要问题。如果病人自己的骨髓可以在体外变成非白细胞性，然后在放化疗完成后重新注入病人体内，这两个问题都可以避免。在这里，我们描述了一个模型系统，其中致命的照射大鼠注射骨髓细胞和白血病细胞的混合物，并在其中的发展，白血病在受体大鼠的预防孵育的细胞，注射前，与单克隆抗体-蓖麻毒素共轭物是选择性毒性的白血病细胞。通过在存在乳糖的情况下进行孵育，可以阻断缀合物对造血干细胞的非特异性毒性，乳糖竞争性拮抗缀合物的蓖麻毒蛋白部分与细胞表面半乳糖残基的结合1 -3。
Graft-versus-host disease and marrow graft rejection are two major problems in the treatment of leukaemia with whole body irradiation, high-dose chemotherapy and bone marrow transplantation. Both these problems could be avoided if the patient's own bone marrow could be rendered aleukaemic in vitro and then reinjected into the patient after the radio-chemotherapy had been completed. Here we describe a model system in which lethally irradiated rats were injected with a mixture of bone marrow cells and leukaemic cells and in which the development of leukaemia in the recipient rats was prevented by incubating the cells, before injection, with a monoclonal antibody–-ricin conjugate that was selectively toxic to the leukaemic cells. Nonspecific toxicity of the conjugate to haematopoietic stem cells was blocked by carrying out the incubation in the presence of lactose which competitively antagonized the binding of the ricin moiety of the conjugate to galactose residues on the cell surface1–3.