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丝裂霉素与抗甲胎蛋白抗体的偶联物:对裸鼠体内移植的产甲胎蛋白人胃癌的抗肿瘤作用

Conjugates of mitomycin with anti-alpha-fetoprotein antibody: antitumor effect against alpha-fetoprotein-producing human gastric carcinoma implanted in nude mice.

作者信息

Takahashi Y, Mai M, Umemoto N, Kato Y, Hara T, Tsukada Y

出版信息

NCI Monogr. 1987(3):101-5.

PMID:2434869
Abstract

Conjugates of mitomycin (MMC) with an affinity-purified horse anti-human alpha-fetoprotein (AFP) antibody were prepared by direct conjugation or by indirect conjugation mediated by human serum albumin; 1a-[4-(N-succinimidoxycarbonyl)butyryl]-MMC was used in the preparation. In therapeutic experiments with athymic nude mice inoculated with the human AFP-producing gastric carcinoma OSS, the conjugates caused a greater inhibition of the tumor growth than did an unconjugated mixture of anti-AFP antibody and MMC or similar conjugates with normal horse immunoglobulin. The AFP serum level and its ratio to tumor volume were low in the group of mice treated with anti-AFP conjugate. The enhanced drug activity of the anti-AFP conjugates was not observed against human gastric carcinoma YSS (no AFP production) in nude mice; this suggests the involvement of the specific antibody-antigen interaction in the activity of the anti-AFP conjugates.

摘要

通过直接偶联或由人血清白蛋白介导的间接偶联制备丝裂霉素(MMC)与亲和纯化的马抗人甲胎蛋白(AFP)抗体的偶联物;制备过程中使用了1a-[4-(N-琥珀酰亚胺氧基羰基)丁酰]-MMC。在用接种了产生人AFP的胃癌OSS的无胸腺裸鼠进行的治疗实验中,与未偶联的抗AFP抗体和MMC混合物或与正常马免疫球蛋白的类似偶联物相比,偶联物对肿瘤生长的抑制作用更强。用抗AFP偶联物治疗的小鼠组中,血清AFP水平及其与肿瘤体积的比值较低。在裸鼠中,未观察到抗AFP偶联物对人胃癌YSS(不产生AFP)的药物活性增强;这表明特异性抗体-抗原相互作用参与了抗AFP偶联物的活性。

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