去甲斑蝥素用于单克隆抗体为载体的肿瘤导向治疗实验研究

用单抗３Ａ５制备与去甲斑蝥素（ＮＣＴＤ）的偶联物。ＥＬＩＳＡ检测结果表明：３Ａ５ ＮＣＴＤ偶联物保持对人肝癌ＢＥＬ ７４０２细胞的免疫反应性。克隆生成法测定结果显示：３Ａ５ ＮＣＴＤ具有比ＮＣＴＤ更强的细胞毒性，两者的ＩＣ５０分别为２．３ｍｇ／Ｌ和４．２ｍｇ／Ｌ。小鼠腹腔内移植Ｈ２２肝癌，腹膜内给药（ｉｐ），３Ａ５ ＮＣＴＤ（３ｍｇ／ｋｇ）和ＮＣＴＤ（３ｍｇ／ｋｇ）的延长寿命值（ＩＬＳ）分别为１６８％和４２％。裸鼠移植人肝癌ＢＥＬ ７４０２细胞，静脉给药（ｉｖ），ＮＣＴＤ的肿瘤抑制率为１５％（Ｐ＞０．０５），３Ａ５ ＮＣＴＤ为６２％（Ｐ＜０．０１）；瘤结周围给药（ｐｔ），ＮＣＴＤ的肿瘤抑制率为４７％（Ｐ＜０．０５），３Ａ５ ＮＣＴＤ为７８％（Ｐ＜０．０１）。结果表明，与ＮＣＴＤ相比，３Ａ５ ＮＣＴＤ对裸鼠移植人肝癌和腹腔肿瘤具有更强的治疗作用。以上结果提示单抗与ＮＣＴＤ偶联物在肿瘤的导向治疗中有较好的疗效。

Use of Monoclonal Antibody Norcantharidin Conjugate in Experimental Targeting Therapy of Tumor

A rat monoclonal antibody was linked to norcantharidin (NCTD), an antitumor drug currently in clinical use McAb 3A5. The 3A5 NCTD conjugate retained complete immunoreactivity of McAb 3A5 to human hepatoma cancer BEL 7402 cells. The IC 50 values of 3A5 NCTD and free NCTD were 2.3 mg/L and 4.2 mg/L, respectively. The 3A5 NCTD showed higher cytotoxicity than free NCTD. Hepatoma H22 ascites was transplanted into the peritoneal of mice. 3A5 NCTD or NCTD were injected into the cavity. The ILS(%) values were 168% and 42%. Tumor fragments of human hepatoma BEL 7402 were transplanted into nude mice. Then 3A5 NCTD or NCTD was injected iv, or pt(peritumorally). The inhibition rates on the growth of hepatoma BEL 7402 xenografts were 62% and 15% for iv; 78% and 47% for pt.Results indicate that 3A5 NCTD is highly effective against targeted human cancer xenograft and mouse tumor.