We have recently established a
cancer-reactive human
monoclonal antibody, GAH, with a positive ratio of over 90% against
stomach cancer. GAH was formulated as polyethyleneglycol (PEG)-modified immunoliposomal
doxorubicin (DXR) (ILD) and its efficacy was examined against gastrointestinal human
cancers. In in vitro studies, a comparison of ILD with PEG-modified liposomal DXR (LD) demonstrated that ILD had dose-dependent cytotoxicity for GAH-reactive B37
cancer cells, but not LD. In concordance with this result, microscopic observations showed that ILD was bound to and GAH-dependently internalised by B37 cells. In in vivo studies, ILD exhibited significantly greater antitumour activity on
cancer xenograft models than LD or free DXR. The relation between efficacy and
antigen density was examined on 10 xenograft models bearing
cancer cells with varying GAH reactivity. Immunoliposomal
doxorubicin therapeutic activity correlated with the
antigen density, with a minimum number being required. Also, ILD revealed strong antitumour activity on
cancers with low sensitivity to DXR or LD, suggesting that ILD overcame the DXR resistance of
antigen-positive
cancer cells. Thus, these results show that GAH endows
liposomes with targeting activity, resulting in strong efficacy against
gastrointestinal cancers.