Antitumour activity of a sterically blocked ricin immunotoxin on a human colorectal adenocarcinoma grafted subcutaneously in nude mice
Antitumour activity of a sterically blocked ricin immunotoxin on a human colorectal adenocarcinoma grafted subcutaneously in nude mice
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空间阻断蓖麻毒素免疫毒素对裸鼠皮下移植人结直肠腺癌的抗肿瘤活性
DOI：
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
L. Cattel
中科院分区：
文献类型：
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作者：
P. Brusa;F. Dosio;F. Pietribiasi;L. Delprino;Paola Feraiorni;M. Mariani;G. Bussolati;L. Cattel
我们制备了一种蓖麻毒素-抗体结合物，它缺乏与Sepharose6B的半乳糖基残基结合的能力，Sepharose6B是一种所谓的封闭免疫毒素。单抗AR-3通过硫醚键与蓖麻毒素发生交联反应。进一步的研究表明，免疫结合物抑制了裸鼠体内移植的HT-29细胞的生长，没有表现出任何不良的蓖麻毒素毒性。在本工作中，我们首先评价了AR-3-蓖麻毒素结合物对荷瘤小鼠的药代动力学行为和生物分布。静脉注射的免疫结合物的行为几乎介于抗体和蓖麻毒素之间。此外，当免疫毒素静脉注射到荷有皮下肿瘤的裸鼠身上时，由于免疫毒素从血液到皮肤的渗透性相对较低，因此没有治疗效果。相反，瘤周治疗可使肿瘤结节显著减少，而不会使恶性细胞大量再生。这一结果也是在对一个公认的肿瘤进行免疫毒素治疗时取得的。这一发现严格地与免疫结合物的特异性有关，因为用无关的免疫毒素进行类似的治疗显示治疗失败。
SummaryWe prepared a ricin-antibody conjugate, lacking the ability to bind the galactosidic residues of Sepharose 6B, a so-called blocked immunotoxin. The monoclonal antibody AR-3 was cross-linked to ricin through a thioether bond. Further studies showed that the immunoconjugate suppressed the tumour growth of HT-29 cells in intraperitoneally grafted nude mice, without showing any undesirable ricin toxicity.In this work, to demonstrate the therapeutic activity of the AR-3—ricin conjugate injected into mice bearing subcutaneous tumour, we first evaluated its pharmacokinetic behaviour and biodistribution. The behaviour of the immunoconjugate injected intravenously was almost intermediate between that of the antibody and ricin. Moreover, when the immunotoxin was intravenously administered to nude mice bearing subcutaneous tumour, no therapeutic effects appeared, in accordance with the relatively low permeability of the immunotoxin from the blood to the skin. In contrast, peritumoral treatment produced a strong reduction of the neoplastic nodules without substantial regrowth of the malignant cells. This result was also achieved when the immunotoxin treatment was performed on a well-established tumour. This finding was strictly related to the specificity of the immunoconjugate, since the analogous treatment with an irrelevant immunotoxin showed therapeutic failure.
一种免疫毒素，由单克隆抗转铁蛋白受体抗体组成，通过二硫键与核糖体失活蛋白 gelonin 连接：在体外和体内对人类肿瘤具有有效作用。
DOI：
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发表时间：
1987
期刊：
Journal of the National Cancer Institute
影响因子：
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作者：
ScottJr,CF;Goldmacher,VS;Lambert,JM;Jackson,JV;McIntyre,GD
通讯作者：
McIntyre,GD
荷瘤小鼠中肿瘤反应性免疫毒素的药代动力学：抗体效价和蓖麻毒素 A 链去糖基化对清除和肿瘤定位的影响。
影响因子：
11.2
作者：
Fulton,RJ;Tucker,TF;Vitetta,ES;Uhr,JW
通讯作者：
Uhr,JW