双功能抗体用于肝癌导向治疗的实验研究

Targeting treatment of human HCC xenografts im-planted in nude mice using bifunctional antibody HC-1 combined with mitomycin C

在获得抗人肝癌单克隆抗体及抗丝裂霉素单克隆抗体的基础上，用化学交联法制备双功能抗体，双功能抗体保持了原二个单克隆抗体的特异性，在放射免疫显像中获得良好的肿瘤显像，其肿瘤与非肿瘤的放射比为８．４０±０．４５，显著高于对照组（１．２１±０．１２，Ｐ＜０．０１），在实验性治疗中，双功能抗体组６０％的荷瘤鼠（ｎ＝１０）生存超过６０天，而二个对照组分别在３０天、５６大全部死亡。结果表明，双功能抗体是导向治疗较为理想的载体之一。

ifunctional antibody (BFA) HCI possessingone binding site for mitomycin C (MMC) and a com-panion site directed against human hepatocellular car-cinoma (HCC) cell niembrane was constructed bychemical conjugation of two Fab’fragments of McAbMMCI and McAb HCMP-1. BFA could be specifically attached totumor xenograft of nude mice bearing human HCC and thus simultaneouslyr capiure mitomycin C. The attachment of these complexs was detected by radioimniunoimaging in nude mice bearinghunian HCC using 131-I labelled BFA HC-1. Clearimaging of the tumor was obtained in 6 days after i.p. injection. On the Sth day after the injection, tu-morlliver (T/L) ratio was 8. 04 ±0. 45. When theBFA HC-1 was used to be combined with MMC forthe targeting treatment of huruan HCC implanted innude mice, the highly significant suppression of tu-nior growth was achieved. After two months oftreatment, xenografts of 40% (4/10) mice disa-peared and 60% (6/10) of the mice survived. Thosernice treated only with MMC became more and moresick even if the grafted tumors shrank, and all ofthern died wrthin 2 months after therapy. The con-trols were treated with nonspecific IgG. Tumorsgrew very fast, and most of the controls died in month after the first injection. The results suggcstthat BFA HCI could concentrate MMC on the hu-man HCC cells, and it is a kind of suitable carrier forthe targeting treatment of human HCC.