Bolognesi A, Tazzari P L, Olivieri F, Polito L, Lemoli R, Terenzi A, Pasqualucci L, Falini B, Stirpe F
Dipartimento di Patologia Sperimentale, Università di Bologna, Italy.
Br J Haematol. 1998 Apr;101(1):179-88. doi: 10.1046/j.1365-2141.1998.00665.x.
Immunotoxins were prepared with three ribosome-inactivating proteins (RIP), momordin, pokeweed antiviral protein from seeds (PAP-S) and saporin-S6, linked to the anti-CD22 monoclonal antibody OM124. These immunotoxins inhibited protein synthesis by CD22-expressing cell lines Daudi, EHM, BJAB, Raji and BM21 with IC50 (concentration causing 50% inhibition) ranging from < 5 x 10(-15) to 7.6 x 10(-11) M as RIP, and IC90 (concentration causing 90% inhibition) ranging from 5 x 10(-14) to 5 x 10(-8)M, with no effect on a CD22-negative HL60 cell line at the highest concentration tested (5 x 10[-8] M). Apoptosis was induced in sensitive cells. The formation of bone marrow colonies was inhibited by no more than 40% by the immunotoxins at concentrations up to 10(-9) M. Treatment with the immunotoxins, alone or in combination, significantly extended the survival time of mice bearing transplanted Daudi cells. A treatment with cyclophosphamide and OM124/saporin immunotoxin was particularly effective in SCID mice transplanted with a low number of cells (3 x 10[-6]), when 60% of the animals remained tumour-free.
用三种核糖体失活蛋白（RIP）——苦瓜素、种子商陆抗病毒蛋白（PAP-S）和皂草素-S6，与抗CD22单克隆抗体OM124连接，制备了免疫毒素。这些免疫毒素抑制表达CD22的细胞系Daudi、EHM、BJAB、Raji和BM21的蛋白质合成，其半数抑制浓度（IC50，即引起50%抑制的浓度）范围为<5×10⁻¹⁵至7.6×10⁻¹¹M（以RIP计），90%抑制浓度（IC90）范围为5×10⁻¹⁴至5×10⁻⁸M，在最高测试浓度（5×10⁻⁸M）下对CD22阴性的HL60细胞系无影响。敏感细胞中诱导了凋亡。在浓度高达10⁻⁹M时，免疫毒素对骨髓集落形成的抑制作用不超过40%。单独或联合使用免疫毒素治疗，显著延长了移植Daudi细胞的小鼠的存活时间。当60%的动物无肿瘤时，环磷酰胺和OM124/皂草素免疫毒素联合治疗对移植少量细胞（3×10⁻⁶）的SCID小鼠特别有效。
