宫颈癌单克隆抗体-葡聚糖-氨甲喋呤偶合物的制备及其体外抗肿瘤作用

Preparation of a monoclonal antibody (AU_(14-1))—methotrexate (MTX) conjugate and it's in vitro antitumor activity

以葡聚糖(Dex)氧化产物多醛基葡聚糖作为中间载体,将氨甲喋呤(MTX)共价偶联于抗小鼠宫颈癌单克隆抗体AU_(14-1)(IgG)上,制得AU_(14-1)-Dex-MTX偶合物;其中IgG与MTX摩尔比为1:20。间接膜免疫荧光试验表明,偶合物中AU_(14-1)对靶肿瘤U_(14)细胞的特异结合活性在3.75×10^(-8)M水平,与未偶合的AU_(14-1),相似。体外抗肿瘤实验表明,偶合物不仅获得了由单克隆抗体导向的选择性药物抗肿瘤作用,且对HeLa细咆的生长抑制作用强于U_(14)细胞,进一步证明了“进化抗原”理论。本研究提示AU_(14-1)-Dex-MTX偶合物具有临床应用的潜在性。

Methotrexate (MTX)was linked covalently to monoclonal IgG antibody (AU_(14-1)) to a mouse uterine cervical cancer with the use of dextran T-40 as the intermediate carrier. The molar ratio of IgG: MTX was 1: 20 in the conjugate. The conjugate retained full antibody binding activity at the AU_(14-1) concentration of 3.75×10^(-8) M measured by an indirect membrane immunofluorescence assay. The in vitro experiments confirmed that the conjugate not only showed target-selective antitumor effecacy but also was proved to be more effective in inhibiting the growth of HeLa cells than the effect of U_(14) cells, so that it confirmed the 'evolutionary antigen' theory. It is suggested that AU_(14-1)-Dex-MTX conjugate may have good potentiality in clinical application.