The previous pessimistic view of
monoclonal antibodies as
cancer therapeutics was largely influenced by the negative results of multiple clinical trials initiated shortly after the introduction of hybridoma technology. Although murine
antibodies are of value in
cancer therapy, their effectiveness is limited because murine
monoclonal antibodies have a short survival time in humans and induce an immune response that neutralizes their
therapeutic effect. Furthermore, the responses induced by murine
antibodies are limited because they only weakly recruit human effector elements. To circumvent these problems, genetically engineered
antibodies were produced which were mouse-human chimeric
monoclonal antibodies and
humanized antibodies. These
antibodies combine the murine variable or hypervariable regions with the human constant or constant and variable framework regions. Numerous published studies demonstrate that erbB-2
oncogene product overexpression is a frequent cause of breast, ovarian, lung, and
gastric cancers. Recently, an anti-erbB-2 humanized
monoclonal antibody has been generated and used in clinical trials with high clinical response rates. We generated the anti-erbB-2 mouse-human chimeric
monoclonal antibody CH401, which was able to kill
cancer cells. An analysis of the mechanism of its
tumor growth inhibition revealed that the cytotoxicity was induced by apoptosis. This cytotoxic mechanism is not the same a that of other anti-erbB-2
antibodies previously reported.