Tazzari P L, Bolognesi A, De Totero D, Lemoli R M, Fortuna A, Conte R, Crumpton M J, Stirpe F
Servizio di Immunoematologia e Trasfusionale, Policlinico S. Orsola, Bologna, Italy.
Br J Haematol. 1994 Jan;86(1):97-105. doi: 10.1111/j.1365-2141.1994.tb03258.x.
In this study we describe immunotoxins prepared with different CD2 monoclonal antibodies (mAbs) and a ribosome-inactivating protein, saporin. The CD2 immunotoxins were tested on different models. Anti-CD2-saporin conjugates inhibited protein synthesis by a neoplastic CD2+ cell line (SKW-3) and by an interleukin 2 dependent polyclonal CD2+ lymphoid cell culture (T lymphoblasts), with IC50s ranging from 10(-13) M to 10(-11) M (as saporin). Similar results were obtained with proliferation inhibition tests (3H-thymidine incorporation) on phytohaemagglutinin (PHA) driven lymphoid cultures and on mixed lymphocyte culture activated lymphocytes. Moreover a CD2-ricin A chain conjugate was less effective than an analogous immunotoxin containing the same CD2 mAb and saporin in inhibiting lymphocyte proliferation induced by PHA (IC50 approximately 10(-9) M as ricin A chain versus 10(-12) M as saporin). The conjugates were not toxic on bone marrow stem cells. These results suggest that CD2-saporin immunotoxins could represent an effective tool for CD2+ lymphomas or leukaemias, and for T-dependent immune disorders, such as transplanted organ rejection and graft-versus-host disease.
在本研究中，我们描述了用不同的CD2单克隆抗体（mAb）和一种核糖体失活蛋白——皂草素制备的免疫毒素。对不同模型测试了CD2免疫毒素。抗CD2-皂草素偶联物抑制了肿瘤性CD2+细胞系（SKW-3）和白细胞介素2依赖性多克隆CD2+淋巴细胞培养物（T淋巴母细胞）的蛋白质合成，IC50范围为10^(-13)M至10^(-11)M（以皂草素计）。在用植物血凝素（PHA）驱动的淋巴细胞培养物和混合淋巴细胞培养激活的淋巴细胞上进行的增殖抑制试验（3H-胸腺嘧啶核苷掺入）中也得到了类似结果。此外，在抑制PHA诱导的淋巴细胞增殖方面，CD2-蓖麻毒素A链偶联物比含有相同CD2 mAb和皂草素的类似免疫毒素效果差（以蓖麻毒素A链计IC50约为10^(-9)M，以皂草素计为10^(-12)M）。这些偶联物对骨髓干细胞无毒。这些结果表明，CD2-皂草素免疫毒素可能是治疗CD2+淋巴瘤或白血病以及T细胞依赖性免疫疾病（如移植器官排斥和移植物抗宿主病）的有效工具。
