药物与抗AFP抗体联接物治疗晚期肝癌Ⅰ期临床试验

PHASE I CLINICAL TRAIL OF DRUG-ANTIBODY CONJUGATES IN PATIENTS WITH ADVANCED HEPATOCARCINOMA——A PRELIMINARY REPORT

抗人AFP IgG分别与5-Fu、MMC和PDD联接成的化学免疫联接物,治疗经病理诊断的原发性肝癌21例。病人接受AFP IgG蛋白量12.75～355.5mg,平均117.5mg。结果肝占位病变缩小28.5％,血清AFP下降52.3％(其中转阴14.2％),症状改善22.2％。治后一年生存率19％,中位生存期5.7月。毒副反应:白细胞减少19％,血小板减少4.7％,血清SGPT升高23.8％。对心肾功能无影响。治疗期间及停药60天观察无任何变态反应出现,观察结果表明:以马抗人AFP抗体与化疗药物联接,制备的生物“导弹”,临床应用安全,可以进入Ⅱ期临床试验。

The horse anti-human Alpha fetoprotein (AFP) antibody was respeotively conju-gated with mitomycin O, 5-Fu or PDD by direct conjugation with glutoraldehyde. Thekilling rate .of immunoconjugates on AFP positive human liver coancer cell line(Alexan-der and Q3) was significantly higher than that of free drug in vitro. However,the immunoconjugates showed very low cytotoxioity to AFP negative K562 cell line.Immunodiffusion test revealed that the immunoreactivity of immunoconjugates waswell retained after conjugation. In a phase I clinical study immunoconjugates woreadministered via the hepatic artery or intravenously to twenty one patients withinoperable and AFP positive primary hepatocellular carcinoma histologically confirmed.Patients had been received antibody protein range 12 .75--355. 5mg (average 117. 5mg).After treatment the subjective improvoment was 22.2%,serum AFP level decreasing52 .3%,tumor regression 28. 5%. The side effect, if any,was minimal. Neither serumsickness nor clinical manifestation of kidney damage had been observed.