抗人肺腺癌单克隆抗体与N-乙酰消瘤芥结合物的制备及其选择性细胞毒的研究

Preparation and in Vitro Selective Cytotoxicity of Conjugate of N-acetylnitrocaphane with marine Monoclonal Antibody Against Human Lung Adenocarcinoma Cell Line

本文报道了鼠抗人肺腺癌单克隆抗体-N-乙酰消瘤芥结合物的制备及其对肿瘤靶细胞的杀伤作用,经化学修饰后的N-乙酰消瘤芥活性酯与抗体偶合,结合物的克分子结合比为1:79,且不影响抗体活力,在相似浓度下比较了单抗结合物、单抗、正常鼠IgG及其结合物与药物对靶细胞的毒性试验。结果表明:单抗结合物能显著抑制[~3H]-胸腺嘧啶核苷参入细胞量,其抑制率分别为92％、60％、40％、45％与15％。提示N-乙酰消瘤芥单抗结合物的抑制作用是由单抗导向的。

In this paper we reported that the conjugate of N-acetylnitrocaphane with marine monoclonal antibody against human lung adrenocarcinoma cell (LAC-210) was prepared and its in vitro cytotoxicity on human lung adrenocarcinoma cell line (SPC-A-1) was determined. Nitrocaphane, a pontent anti-cancer agent, was acetylation with N-succiniminoacetale to protect the amino group. The acetylnitrocaphane was then treated with N-hydroxysuccimide and dicyclohexylcarbodiimide to produce N-acetylni-trocaphane acetive ester, which was coupled to monoclonal antibody. The molar ratio of monoclonal antibody : N-acetylnitrocaphane in the conjugate was 1 : 79. Then in vitro cytotoxicity of the conjugate was tested by the inhibition of (3H)-TDR incorporation into tumor cells, which demonstrated that the conjugate wae specifically cytotoxic toward antibady-reactive cell lines, having more activity than free drug.