Kato Y, Umemoto N, Kayama Y, Fukushima H, Takeda Y, Hara T, Tsukada Y
J Med Chem. 1984 Dec;27(12):1602-7. doi: 10.1021/jm00378a013.
In studies on antitumor antibody-cytotoxic drug conjugates as potential antitumor agents with improved tumor specificity, daunomycin (DM) was first linked to a poly-L-glutamic acid (PLGA) derivative having a single masked thiol group. At the thiol group, DM-linked PLGA was bound to horse anti-rat alpha-fetoprotein (AFP) antibody. The anti-AFP antibody-PLGA-DM conjugate (anti-AFP conjugate, DM/PLGA/Ig molar binding ratio, 7.5/1.2/1.0) retained most of the antigen-binding activity of the parent antibody and was more potent than either unconjugated DM, a conjugate similarity prepared with normal horse immunoglobulin (normal conjugate), or an unconjugated mixture of anti-AFP antibody and DM in an in vitro cytotoxicity assay against the AFP-producing rat ascites hepatoma cell line AH66. Anti-AFP conjugate tended to be less cytotoxic than DM against the AFP-nonproducing rat ascites hepatoma AH272 cells, and in this case there was no difference between the cytotoxicities of anti-AFP conjugate and of normal conjugate.
在关于抗肿瘤抗体 - 细胞毒性药物偶联物作为具有更高肿瘤特异性的潜在抗肿瘤药物的研究中，柔红霉素（DM）首先与具有单个掩蔽硫醇基团的聚 - L - 谷氨酸（PLGA）衍生物相连。在硫醇基团处，与DM相连的PLGA与马抗大鼠甲胎蛋白（AFP）抗体结合。抗AFP抗体 - PLGA - DM偶联物（抗AFP偶联物，DM/PLGA/Ig摩尔结合比为7.5/1.2/1.0）保留了亲本抗体的大部分抗原结合活性，并且在针对产生AFP的大鼠腹水肝癌细胞系AH66的体外细胞毒性试验中，比未偶联的DM、用正常马免疫球蛋白制备的类似偶联物（正常偶联物）或抗AFP抗体与DM的未偶联混合物更有效。抗AFP偶联物对不产生AFP的大鼠腹水肝癌AH272细胞的细胞毒性往往比DM小，在这种情况下，抗AFP偶联物和正常偶联物的细胞毒性没有差异。
