Paprocka M, Wiedlocha A, Radzikowski C
Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw.
In Vivo. 1990 May-Jun;4(3):209-13.
In an attempt to eliminate selectively mouse L1210V leukemic cells from infiltrated bone marrow, the immunotoxin MoAb-16-RTA composed of monoclonal antibody recognizing oncofetal antigen on L1210V cells and the ricin A chain was prepared. The immunotoxin exhibited an antigen-specific, dose-dependent cytotoxic effect in vitro. One hour's exposure of leukemic cells to 10(-6) M of immunotoxin appeared to be sufficient to kill all leukemic cells. In the experimental conditions applied, a complete elimination of L1210V cells from leukemic bone marrow was achieved. MoAb-16 antibody and complement in the same experimental protocol, the bone marrow purging was not complete. The surviving leukemic cells were still able to grow and kill recipient mice. The in vitro exposure to immunotoxin or to antibody and complement was not toxic to normal bone marrow progenitors. The exposure of leukemic cells to selected cytostatic agents of the oxazaphosphorine group appeared to be effective in the elimination of leukemic cells, but doses required for killing leukemic cells were highly toxic to normal bone marrow progenitors.
为了从浸润的骨髓中选择性清除小鼠L1210V白血病细胞,制备了由识别L1210V细胞上癌胚抗原的单克隆抗体和蓖麻毒素A链组成的免疫毒素MoAb-16-RTA。该免疫毒素在体外表现出抗原特异性、剂量依赖性细胞毒性作用。白血病细胞暴露于10(-6)M免疫毒素1小时似乎足以杀死所有白血病细胞。在所应用的实验条件下,白血病骨髓中的L1210V细胞被完全清除。在相同实验方案中使用MoAb-16抗体和补体时,骨髓净化并不完全。存活的白血病细胞仍能够生长并杀死受体小鼠。体外暴露于免疫毒素或抗体及补体对正常骨髓祖细胞无毒。白血病细胞暴露于恶唑磷类的某些细胞抑制剂似乎对清除白血病细胞有效,但杀死白血病细胞所需的剂量对正常骨髓祖细胞毒性很大。