Porro G, Bolognesi A, Caretto P, Gromo G, Lento P, Mistza G, Sciumbata T, Stirpe F, Modena D
Italfarmaco Research Centre, (Mi), Italy.
Cancer Immunol Immunother. 1993 May;36(5):346-50. doi: 10.1007/BF01741174.
An anti-CD5 monoclonal antibody (mAb) was linked to the plant toxin momordin, a type-1 ribosome-inactivating protein purified from Momordica charantia. The in vitro cytotoxicity of the immunotoxin was evaluated as the inhibition of protein and/or DNA synthesis on isolated peripheral blood mononuclear cells (PBMC) and on human T cell leukemia Jurkat. The potency of the immunotoxin on PBMC was very high (IC50 = 1 - 10 pM) and was not affected by blood components. The conjugate was also very efficient in the inhibition of the proliferative response in a mixed lymphocyte reaction (IC50 = 10 pM). Moreover, the in vitro performance of the immunotoxin compared favorably with those reported for other anti-CD5-based immunoconjugates containing ricin A chain. The in vivo activity of the immunotoxin was assessed in the model of nu/nu mice bearing Jurkat leukemia. A significant inhibition of the tumour development (80%, P < 0.01) in the animals treated with immunotoxin was observed. Taken together, the in vitro and in vivo results suggest that the anti-CD5-momordin conjugate may be useful for graft-versus-host disease therapy and potentially in the treatment of CD5-positive leukemias and lymphomas.
一种抗CD5单克隆抗体（mAb）与植物毒素苦瓜素相连，苦瓜素是从苦瓜中纯化得到的1型核糖体失活蛋白。该免疫毒素的体外细胞毒性通过对分离的外周血单核细胞（PBMC）和人T细胞白血病Jurkat细胞上蛋白质和/或DNA合成的抑制作用来评估。该免疫毒素对PBMC的效力非常高（IC50 = 1 - 10 pM），且不受血液成分影响。该缀合物在混合淋巴细胞反应中对增殖反应的抑制也非常有效（IC50 = 10 pM）。此外，该免疫毒素的体外性能优于其他含蓖麻毒素A链的基于抗CD5的免疫缀合物的报道。在携带Jurkat白血病的裸鼠模型中评估了该免疫毒素的体内活性。观察到用免疫毒素治疗的动物肿瘤发展受到显著抑制（80%，P < 0.01）。综上所述，体外和体内结果表明，抗CD5 - 苦瓜素缀合物可能对移植物抗宿主病治疗有用，并且可能用于治疗CD5阳性白血病和淋巴瘤。
