Hata Y, Takada N, Sasaki F, Abe T, Hamada H, Takahashi H, Uchino J, Tsukada Y
First Department of Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
J Pediatr Surg. 1992 Jun;27(6):724-7. doi: 10.1016/s0022-3468(05)80101-0.
The effect of immunotargeting chemotherapy for hepatoblastoma (HB) and hepatocellular carcinoma (HCC) following the application of adriamycin (ADM) or cis-platinum conjugated with anti-alpha-fetoprotein (AFP) antibody was evaluated experimentally and clinically. The conjugate was made from mouse monoclonal antihuman AFP antibody linked to ADM or CDDP, with a weight ratio of 2.5:1 via a dextran bridge. Experimentally, AFP-producing human HCC transplanted subsequently on nude mice was used. A mixture of the antibody and ADM or CDDP was prepared with the same ratio. Each drug was injected intraperitoneally, three times at the total dose of 14.4 mg/kg as ADM and one time at the dose of 8 mg/kg as CDDP. Tumor growth was inhibited significantly in the conjugate group compared with the other mixture group, the ADM or CDDP group, and the control group. Clinically, the conjugates were administered intraarterially in 4 cases (2 HBs and 2 HCCs) and intravenously in one case (1 HB). ADM and CDDP conjugated with anti-AFP antibody were used in 2 cases and 3 cases, respectively. Antitumor effects from the viewpoint of volume suppression rate showed partial response in 2 cases and no change in 3 cases. The immunotargeting chemotherapy using anti-AFP monoclonal antibodies may be a promising method for treatment of malignant epithelial liver cancer in children.
评估了阿霉素(ADM)或顺铂与抗甲胎蛋白(AFP)抗体结合后对肝母细胞瘤(HB)和肝细胞癌(HCC)进行免疫靶向化疗的效果,并进行了实验和临床研究。该偶联物由与ADM或顺铂(CDDP)连接的小鼠单克隆抗人AFP抗体制成,通过葡聚糖桥连接,重量比为2.5:1。实验中,使用随后移植到裸鼠身上的产AFP的人肝癌细胞。以相同比例制备抗体与ADM或CDDP的混合物。每种药物经腹腔注射,ADM总剂量为14.4mg/kg,分三次注射,CDDP剂量为8mg/kg,注射一次。与其他混合物组、ADM或CDDP组以及对照组相比,偶联物组的肿瘤生长受到显著抑制。临床上,4例患者(2例HB和2例HCC)经动脉给予偶联物,1例患者(1例HB)经静脉给予。分别有2例和3例患者使用了与抗AFP抗体偶联的ADM和CDDP。从体积抑制率来看,抗肿瘤效果显示2例部分缓解,3例无变化。使用抗AFP单克隆抗体进行免疫靶向化疗可能是治疗儿童恶性上皮性肝癌的一种有前景的方法。