Tsukada Y, Hurwitz E, Kashi R, Sela M, Hibi N, Hara A, Hirai H
Proc Natl Acad Sci U S A. 1982 Dec;79(24):7896-9. doi: 10.1073/pnas.79.24.7896.
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 were coupled via a dextran bridge to daunomycin. Both types of conjugates were tested in vitro and in vivo for their anti-tumor activity. They were equally cytotoxic to rat AH66 hepatoma cell line in culture. Rats challenged with hepatoma cells were treated with the conjugates either by intraperitoneal or intravenous injections. Daunomycin conjugates with horse anti-AFP and monoclonal mouse anti-AFP were capable of delaying the tumor development more efficiently than the controls of antibodies or free drug, mixtures of drug with antibodies, and a conjugate of drug and normal immunoglobulin. The specific conjugates were considerably more effective when the treatments were given intravenously. The specific conjugates produced 60% long-term survival, whereas the controls delayed only slightly tumor development.
通过将小鼠骨髓瘤细胞与用大鼠甲胎蛋白(AFP)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通过葡聚糖桥与柔红霉素偶联。两种类型的偶联物均在体外和体内测试其抗肿瘤活性。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或静脉注射用偶联物进行治疗。柔红霉素与马抗AFP和单克隆小鼠抗AFP的偶联物比抗体或游离药物、药物与抗体的混合物以及药物与正常免疫球蛋白的偶联物的对照更有效地延迟肿瘤发展。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,而对照仅略微延迟肿瘤发展。