Watson S A, Michaeli D, Grimes S, Morris T M, Crosbee D, Wilkinson M, Robinson G, Robertson J F, Steele R J, Hardcastle J D
Department of Surgery, Queen's Medical Centre, Nottingham, UK.
Int J Cancer. 1995 Apr 10;61(2):233-40. doi: 10.1002/ijc.2910610216.
The neutralising ability of rabbit anti-gastrin-17 (G17) antiserum raised by Gastrimmune, an immunogen constructed of the N-terminal portion of human G17 conjugated to diptheria toxoid (DT), was evaluated. The anti-serum (denoted anti-G17: DT) was shown to displace 125[I] G17 from the gastrin receptors on AR42J cells. The therapeutic effect of the rabbit anti-G17:DT anti-serum was evaluated on a freshly derived human colorectal cancer cell line, AP5, which was shown to express both gastrin receptors and gastrin immunoreactivity as assessed by immunocytochemistry. Rabbit anti-G17:DT anti-serum was shown to block basal in vitro growth of AP5 cells when used at an antigen binding capacity of 3.75 x 10(-9) M. The same dilution of anti-serum completely reversed growth stimulated by human G17 at concentrations of 1 x 10(-10) and 1 x 10(-9) M but did not inhibit growth at 1 x 10(-8) M G17. When AP5 was grown as a xenograft in nude mice, the sensitivity to the proliferative effect of human G17 was maintained. In addition, the basal growth of AP5 xenografts was significantly reduced by i.v. infusion of rabbit anti-G17:DT anti-serum when compared to treatment with rabbit anti:DT control anti-serum. Thus anti-G17:DT antibodies raised by Gastrimmune may be of clinical value in gastrin-sensitive tumours.
对由Gastrimmune产生的兔抗胃泌素-17（G17）抗血清的中和能力进行了评估，Gastrimmune是一种由与人G17 N端部分偶联至白喉类毒素（DT）构建的免疫原。该抗血清（称为抗G17:DT）可从AR42J细胞上的胃泌素受体置换125[I] G17。在一种新建立的人结肠癌细胞系AP5上评估了兔抗G17:DT抗血清的治疗效果，经免疫细胞化学评估显示该细胞系表达胃泌素受体和胃泌素免疫反应性。当以3.75×10(-9) M的抗原结合能力使用时，兔抗G17:DT抗血清可阻断AP5细胞的基础体外生长。相同稀释度的抗血清可完全逆转1×10(-10) M和l×10(-9) M浓度的人G17刺激的生长，但不抑制1×10(-8) M G17刺激的生长。当AP5作为异种移植物在裸鼠体内生长时，对人G17增殖作用的敏感性得以维持。此外，与用兔抗:DT对照抗血清治疗相比，静脉输注兔抗G17:DT抗血清可显著降低AP5异种移植物的基础生长。因此，由Gastrimmune产生的抗G17:DT抗体可能在对胃泌素敏感的肿瘤中具有临床价值。
