Blocked and not blocked whole-ricin-antibody immunotoxins: Intraperitoneal therapy of human tumour xenografted in nude mice
Blocked and not blocked whole-ricin-antibody immunotoxins: Intraperitoneal therapy of human tumour xenografted in nude mice
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阻断和未阻断的全蓖麻毒素抗体免疫毒素：裸鼠异种移植人类肿瘤的腹膜内治疗
DOI：
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
L. Cattel
中科院分区：
文献类型：
--
作者：
P. Brusa;F. Pietribiasi;G. Bussolati;F. Dosio;R. Arione;P. Comoglio;M. Prat;L. Cattel
本工作合成了一种封闭的免疫毒素，它由蓖麻毒素和AR-3单克隆抗体通过短的硫醚键连接而成。该偶联物失去了与Sepharose 6 B的半乳糖苷残基结合的能力，这可能是由于抗体分子对蓖麻毒素B链的空间限制。在体外测定中，免疫毒素仅对表达相应AR-3表位的细胞有活性。通过将其直接注射到荷瘤裸小鼠的腹腔中来评估我们阻断的免疫毒素的体内活性。将动物腹膜内移植HT-29细胞系，该细胞系来源于表达抗原CAR-3的人结肠直肠腺癌，AR-3单克隆抗体针对该抗原。为了达到腹膜内阻断免疫毒素治疗的最佳方案，测试的最佳方案需要在移植后第4天和第6天施用免疫毒素（2 μg）。在随后的不同日期处死小鼠以确定治疗效果。制备不同器官的组织切片，用苏木精/伊红染色，还用AR-3单克隆抗体通过免疫细胞化学方法进行检查，以确认肿瘤细胞表面存在相关抗原。阻断的免疫毒素基本上抑制了移植的HT-29细胞的肿瘤生长，而没有显示出任何不良的蓖麻毒素毒性。最重要的是，建立移植HT-29肿瘤细胞治疗阻断免疫毒素几乎完全消退，而在相同的条件下，不阻断免疫毒素，无关的免疫毒素，蓖麻毒素，和AR-3单独未能抑制肿瘤生长。
SummaryA blocked immunotoxin, consisting of ricin and AR-3 monoclonal antibody joined by a short thioether bond, was previously synthesized. This conjugate had lost the ability to bind the galactosidic residues of Sepharose 6B, probably because of the steric restraint of the antibody molecule on the ricin B chain. In in vitro assays immunotoxin was active only on cells expressing the corresponding AR-3 epitope. The in vivo activity of our blocked immunotoxin was assessed by injecting it directly into the peritoneal cavity of tumour-bearing nude mice. The animals were i.p. grafted with the HT-29 cell line, which was derived from a human colorectal adenocarcinoma expressing the antigen CAR-3, against which the AR-3 monoclonal antibody is directed. The best protocol tested, to arrive at the optimal regimen for the i.p. blocked immunotoxin therapy, required the administration of the immunotoxin (2 μg) on days 4 and 6 after the graft. The mice were killed on different subsequent days to determine the therapeutic effects. Histological sections of the different organs were prepared and stained with haematoxylin/eosin and were also examined by an immunocytochemical method with AR-3 monoclonal antibody to confirm the presence of the relating antigen on the tumour cell surface. The blocked immunotoxin substantially suppressed tumour growth of the grafted HT-29 cells, without showing any undesirable ricin toxicity. Most importantly, established transplanted HT-29 tumour cells treated with blocked immunotoxin almost completely regressed, while under the same conditions the not blocked immunotoxin, an irrelevant immunotoxin, ricin, and the AR-3 alone failed to inhibit tumour growth.
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影响因子：
11.2
作者：
T. C. Hamilton;R. Young;K. G. Louie;B. Behrens;W. Mckoy;K. Grotzinger;R. Ozols
通讯作者：
T. C. Hamilton;R. Young;K. G. Louie;B. Behrens;W. Mckoy;K. Grotzinger;R. Ozols
抗 Mr 67,000 蛋白免疫毒素对裸鼠模型中人类肿瘤的细胞毒性作用。
影响因子：
11.2
作者：
Weil-Hillman,G;Runge,W;Jansen,FK;Vallera,DA
通讯作者：
Vallera,DA
特异性免疫毒素完全抑制人白血病细胞体内生长：裸鼠模型。
DOI：
10.1073/pnas.84.10.3390
发表时间：
1987
影响因子：
11.1
作者：
Hara,H;Seon,BK
通讯作者：
Seon,BK
由 abrin A 链和肝癌相关抗原单克隆抗体组成的有效免疫缀合物对 L10 肝癌细胞具有选择性抗肿瘤作用。
影响因子：
11.2
作者：
Hwang,KM;Foon,KA;Cheung,PH;Pearson,JW;Oldham,RK
通讯作者：
Oldham,RK
影响因子：
11.2
作者：
Weil-Hillman,G;Uckun,FM;Manske,JM;Vallera,DA
通讯作者：
Vallera,DA