A recombinant immunotoxin consisting of two antibody variable domains fused to Pseudomonas exotoxin
A recombinant immunotoxin consisting of two antibody variable domains fused to Pseudomonas exotoxin
复制标题
由与假单胞菌外毒素融合的两个抗体可变结构域组成的重组免疫毒素
作者：
V. Chaudhary;G. Queen;R. Junghans;T. Waldmann;D. FitzGerald;I. Pastan
抗体和生长因子已经与不同的毒素化学偶联，产生细胞毒性分子，选择性杀死携带适当抗原或受体的细胞1，2。使用常规化学偶联技术产生的抗体-毒素缀合物（免疫毒素）具有若干不期望的特征。抗体的最小结合单位是由轻链和重链可变结构域组成的Fv片段。最近，通过将轻链和重链可变结构域与肽接头连接在一起，已经在大肠杆菌X中产生了抗体的活性单链Fv片段3，4。在这里，我们描述了在大肠杆菌中的构建和表达。单链抗体毒素融合蛋白抗Tac（Fv）-PE 40，其中抗Tac（抗人白细胞介素-2受体5 p55亚基的单克隆抗体）的可变区以肽键连接到PE 40（一种缺乏结合域的假单胞菌外毒素的修饰形式）。抗-Tac（Fv）-PE 40对两种白细胞介素-2受体携带的人细胞系具有很强的细胞毒性，但对受体阴性细胞没有细胞毒性。
ANTIBODIES and growth factors have been chemically coupled to different toxins to produce cytotoxic molecules that selectively kill cells bearing appropriate antigens or receptors1,2. Antibody-toxin conjugates (immunotoxins) produced using conventional chemical coupling techniques have several undesirable characteristics. The smallest binding unit of an antibody is an Fv fragment which consists of a light and heavy chain variable domain. Recently, active single chain Fv fragments of antibodies have been produced in Esherichia coli x by attaching the light and heavy chain variable domains together with a peptide linker3,4. Here we describe the construction and expression in E coli. of a single chain antibody toxin fusion protein, anti-Tac(Fv)–PE40, in which the variable regions of anti-Tac, a monoclonal antibody to the p55 subunit of the human interleukin-2 receptor5, are joined in peptide linkage to PE40, a modified form of Pseudomonas exotoxin lacking its binding domain. Anti-Tac(Fv)–PE40 was very cytotoxic to two interleukin-2 receptor-bearing human cell lines but was not cytotoxic to receptor-negative cells.
影响因子：
56.9
作者：
E. Vitetta;R. Fulton;R. May;M. Till;J. Uhr
通讯作者：
E. Vitetta;R. Fulton;R. May;M. Till;J. Uhr
影响因子：
56.9
作者：
BIRD, RE;HARDMAN, KD;WHITLOW, M
通讯作者：
WHITLOW, M
DOI：
10.1073/pnas.85.16.5879
发表时间：
1988-08-01
影响因子：
11.1
作者：
HUSTON, JS;LEVINSON, D;OPPERMANN, H
通讯作者：
OPPERMANN, H