Immunotherapy in nude mice of human hepatoma using monoclonal antibodies against hepatitis B virus

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Abstract
The human hepatoma cell line PLC/PRF/5, which contains integrated hepatitis B virus DNA, synthesises and secretes hepatitis B virus surface antigen (HBsAg). When injected into BALB/c nude mice, these cells produce well-vascularized, encapsulated tumours in almost 100% of animals. HBsAg has been demonstrated on the surface and in the cytoplasm of PLC/PRF/5 cells using immunofluorescence techniques. Recently, we reported that monoclonal antibodies to HBsAg (IgG1, IgG2a and IgM isotypes) bind to HBsAg-associated viral determinants of PLC/PRF/5 cells in culture and immunoprecipitate HBsAg secreted into the growth medium. Also IgG2a and IgM antibodies to HBsAg (anti-HBs) produce specific lysis of PLC/PRF/5 cells in culture in the presence of complement, but have no lytic effect on human hepatoma cells which do not express HBsAg. In the present study, we demonstrate that IgM and IgG2a, but not IgG1, monoclonal anti-HBs specifically prevent or suppress tumour formation in a substantial number of athymic nude mice injected with PLC/PRF/5 cells.