Dinota A, Tazzari P L, Abbondanza A, Battelli M G, Gobbi M, Stirpe F
Istituto di Ematologia L. & A. Seràgnoli, Università di Bologna, Italy.
Bone Marrow Transplant. 1990 Jul;6(1):31-6.
The selective cytotoxicity of the xanthine oxidase conjugated to an 8A monoclonal antibody recognizing a human plasma cell-associated antigen has been described. The selectivity and the toxicity of the hypoxanthine/conjugated xanthine oxidase system was increased by removing the excess of conjugate and by adding chelated iron. Under these experimental conditions the cytotoxicity of the conjugate exceeded that of free xanthine oxidase by one order of magnitude. The conjugate effectively purged bone marrow from infiltrating neoplastic plasma cells and added target Raji cells, provided blood was removed and bone marrow peroxidases were exhausted. In conditions of purging effectiveness the conjugate had no toxicity to CFU-GM. No toxicity to mice was observed after i.v. injection of xanthine oxidase-antibody conjugate up to 2.9 U/kg body weight. Thus the hypoxanthine/conjugated xanthine oxidase system could be an effective and nontoxic tool for the ex vivo bone marrow purging in multiple myeloma patients for autologous transplantation.
已描述了与识别人类浆细胞相关抗原的8A单克隆抗体偶联的黄嘌呤氧化酶的选择性细胞毒性。通过去除过量的偶联物并添加螯合铁，次黄嘌呤/偶联黄嘌呤氧化酶系统的选择性和毒性得以提高。在这些实验条件下，偶联物的细胞毒性比游离黄嘌呤氧化酶高出一个数量级。该偶联物有效地清除了浸润性肿瘤浆细胞的骨髓，并对添加的靶拉吉细胞起作用，前提是去除血液且骨髓过氧化物酶耗尽。在清除有效的情况下，该偶联物对CFU-GM无毒性。静脉注射高达2.9 U/kg体重的黄嘌呤氧化酶-抗体偶联物后，未观察到对小鼠有毒性。因此，次黄嘌呤/偶联黄嘌呤氧化酶系统可能是一种有效且无毒的工具，用于多发性骨髓瘤患者自体移植的体外骨髓净化。
