[Targeting treatment of human HCC xenografts implanted in nude mice using bifunctional antibody HC-1 combined with mitomycin C].

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.