Hattori S, Furuhashi Y, Goto S, Tomoda Y
Nihon Sanka Fujinka Gakkai Zasshi. 1983 Jan;35(1):33-40.
Methotrexate (MTX) was covalently bound to rabbit antibodies (IgG) against hCG and placental alkaline phosphatase (PLALP) by two different methods. By carbodiimide method, 16.9 mols of MTX could be coupled to one mol of IgG, but the antibody activity was completely lost. Whereas, 2.6-3.4 mols of MTX were bound to one mol of IgG and a quarter of original antibody activity was preserved by dextran bridge method. Choriocarcinoma cells BeWo and SCH were exposed to the IgG-MTX conjugates prepared by the latter method for 30 minutes, and the cell growth was investigated. To BeWo, which produces much hCG and less PLALP, anti hCG-IgG-MTX showed a considerable growth inhibition compared to the control groups (p less than 0.05). No effect was observed with anti PLALP-IgG-MTX, nonimmunized IgG-MTX, free MTX and anti hCG-IgG. In contrast, to SCH, which produces much PLALP and less hCG, anti PLALP-IgG-MTX exhibited considerable inhibition (p less than 0.05), whereas anti hCG-IgG-MTX showed no inhibition. Neither anti hCG-IgG-MTX nor anti PLALP-IgG-MTX showed any effect to the endometrial carcinoma cell HEC50B. We concluded that MTX bound to anti hCG-IgG and anti PLALP-IgG have specific growth inhibition effects to the choriocarcinoma cells in vitro, and suggested the possibility of specific immunochemotherapy of this disease.
采用两种不同方法将甲氨蝶呤（MTX）与抗人绒毛膜促性腺激素（hCG）和胎盘碱性磷酸酶（PLALP）的兔抗体（IgG）共价结合。通过碳二亚胺法，1摩尔IgG可偶联16.9摩尔MTX，但抗体活性完全丧失。而通过葡聚糖桥法，1摩尔IgG结合2.6 - 3.4摩尔MTX，且保留了四分之一的原始抗体活性。将绒毛膜癌细胞BeWo和SCH暴露于后一种方法制备的IgG - MTX偶联物30分钟，并研究细胞生长情况。对于产生大量hCG和少量PLALP的BeWo细胞，与对照组相比，抗hCG - IgG - MTX显示出显著的生长抑制作用（p小于0.05）。抗PLALP - IgG - MTX、未免疫的IgG - MTX、游离MTX和抗hCG - IgG均未观察到效果。相反，对于产生大量PLALP和少量hCG的SCH细胞，抗PLALP - IgG - MTX表现出显著抑制作用（p小于0.05），而抗hCG - IgG - MTX未显示抑制作用。抗hCG - IgG - MTX和抗PLALP - IgG - MTX对子宫内膜癌细胞HEC50B均未显示任何作用。我们得出结论，与抗hCG - IgG和抗PLALP - IgG结合的MTX在体外对绒毛膜癌细胞具有特异性生长抑制作用，并提示了针对该疾病进行特异性免疫化疗的可能性。
