Douay L, Gorin N C, Lopez M, Casellas P, Liance M C, Jansen F K, Voisin G A, Baillou C, Laporte J P, Najman A
Cancer Res. 1985 Jan;45(1):438-41.
T101-ricin A-chain immunotoxin is a hybrid molecule made up of the T101 monoclonal antibody bound to the A-chain of ricin. It specifically destroys cells expressing the cell surface T65 antigen. We have designed a preclinical study to evaluate its possible use for the in vitro treatment of T-cell hematological cancers prior to autologous bone marrow transplantation. The data presented here show that conditions previously defined to produce high tumor cell killing, i.e., a 20-hr incubation at 37 degrees in the presence of T101-ricin A-chain immunotoxin up to 10(-7) M in a 10 mM ammonium chloride solution, do not affect the in vitro proliferative capacity of human hematopoietic stem cells studied by means of semisolid medium cultures (granulocyte-macrophage progenitors, burst-forming units-erythrocyte) and continuous liquid cultures (pre-granulocyte-macrophage progenitors). Therefore, autologous bone marrow transplantation with T101-ricin A-chain immunotoxin-treated graft should be feasible.
T101-蓖麻毒素A链免疫毒素是一种由与蓖麻毒素A链结合的T101单克隆抗体组成的杂合分子。它能特异性地破坏表达细胞表面T65抗原的细胞。我们设计了一项临床前研究,以评估其在自体骨髓移植前用于体外治疗T细胞血液系统癌症的可能性。此处呈现的数据表明,先前确定的产生高肿瘤细胞杀伤率的条件,即在10 mM氯化铵溶液中,于37℃存在高达10^(-7) M的T101-蓖麻毒素A链免疫毒素的情况下孵育20小时,并不影响通过半固体培养基培养(粒细胞-巨噬细胞祖细胞、红细胞爆式形成单位)和连续液体培养(前粒细胞-巨噬细胞祖细胞)所研究的人类造血干细胞的体外增殖能力。因此,用T101-蓖麻毒素A链免疫毒素处理过的移植物进行自体骨髓移植应该是可行的。