J.Jpn. Surg. Soc.. 101(9): 607-611, 2000

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Feature topic

ANTIBODY TREATMENT FOR CANCER

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.

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