Wei C, Tang Z Y, Liu K D
Liver Cancer Institute, Shanghai Medical University.
Zhonghua Yi Xue Za Zhi. 1994 Nov;74(11):676-9, 709-10.
Bifunctional antibody (BFA) HC-1 possessing one binding site for mitomycin C (MMC) and a companion site directed against human hepatocellular carcinoma (HCC) cell membrane was constructed by chemical conjugation of two Fab' fragments of McAb MMC-1 and McAb HCMP-1. BFA could be specifically attached to tumor xenograft of nude mice bearing human HCC and thus simultaneously capture mitomycin C. The attachment of these complexes was detected by radioimmunoimaging in nude mice bearing human HCC using 131-I labelled BFA HC-1. Clear imaging of the tumor was obtained in 6 days after i.p. injection. On the 8th day after the injection, tumor/liver (T/L) ratio was 8.04 +/- 0.45. When the BFA HC-1 was used to be combined with MMC for the targeting treatment of human HCC implanted in nude mice, the highly significant suppression of tumor growth was achieved. After two months of treatment, xenografts of 40% (4/10) mice disappeared and 60% (6/10) of the mice survived. Those mice treated only with MMC became more and more sick even if the grafted tumors shrank, and all of them died within 2 months after therapy. The controls were treated with nonspecific IgG. Tumors grew very fast, and most of the controls died in 1 month after the first injection. The results suggest that BFA HC-1 could concentrate MMC on the human HCC cells, and it is a kind of suitable carrier for the targeting treatment of human HCC.
通过化学偶联单克隆抗体MMC - 1和单克隆抗体HCMP - 1的两个Fab'片段，构建了具有一个丝裂霉素C（MMC）结合位点和一个针对人肝细胞癌（HCC）细胞膜的伴随位点的双功能抗体（BFA）HC - 1。BFA可特异性附着于荷有人HCC的裸鼠肿瘤异种移植瘤，从而同时捕获丝裂霉素C。使用131 - I标记的BFA HC - 1通过放射免疫成像在荷有人HCC的裸鼠中检测这些复合物的附着情况。腹腔注射后6天获得清晰的肿瘤图像。注射后第8天，肿瘤/肝脏（T/L）比值为8.04±0.45。当使用BFA HC - 1与MMC联合用于荷有人HCC的裸鼠的靶向治疗时，实现了对肿瘤生长的高度显著抑制。治疗两个月后，40%（4/10）的小鼠异种移植瘤消失，60%（6/10）的小鼠存活。那些仅用MMC治疗的小鼠即使移植瘤缩小但病情越来越重，并且在治疗后2个月内全部死亡。对照组用非特异性IgG治疗。肿瘤生长非常快，大多数对照组在首次注射后1个月内死亡。结果表明，BFA HC - 1可将MMC浓缩于人HCC细胞上，它是一种适合用于人HCC靶向治疗的载体。
