Tsukada Y, Hurwitz E, Kashi R, Sela M, Hibi N, Hara A, Hirai H
Ann N Y Acad Sci. 1983;417:262-9. doi: 10.1111/j.1749-6632.1983.tb32869.x.
Monoclonal antibodies to rat alpha-fetoprotein (AFP) were produced by hybridization of mouse myeloma cells with spleen cells from mice immunized with rat AFP. The monoclonal antibodies as well as horse anti-rat AFP antibodies were coupled via a dextran bridge to daunomycin. Both types of conjugates were tested for their antitumor activity in vitro and in vivo. They were equally cytotoxic to the rat AH66 hepatoma cell line in culture. Rats challenged with hepatoma cells were treated with the conjugates by either intraperitoneal or intravenous injection. Daunomycin conjugates with horse-anti-AFP and monoclonal mouse anti-AFP were capable of delaying the tumor development more efficiently than were the controls of antibodies or free drug, mixtures of drug with antibodies, and a conjugate of drug and normal Ig. The specific conjugates were considerably more effective when the treatments were given intravenously. The specific conjugates produced 60% long-term survival, whereas the controls only slightly delayed tumor development.
通过将小鼠骨髓瘤细胞与用大鼠甲胎蛋白免疫的小鼠脾细胞杂交，制备了抗大鼠甲胎蛋白（AFP）的单克隆抗体。单克隆抗体以及马抗大鼠AFP抗体通过葡聚糖桥与柔红霉素偶联。对这两种偶联物进行了体外和体内抗肿瘤活性测试。它们对培养中的大鼠AH66肝癌细胞系具有同等的细胞毒性。用肝癌细胞攻击的大鼠通过腹腔注射或静脉注射用偶联物进行治疗。与马抗AFP和单克隆小鼠抗AFP偶联的柔红霉素比抗体或游离药物、药物与抗体的混合物以及药物与正常Ig的偶联物等对照更能有效地延缓肿瘤发展。当静脉内给予治疗时，特异性偶联物的效果要显著得多。特异性偶联物产生了60%的长期存活率，而对照仅略微延缓了肿瘤发展。
