Abnormalities of the erbB-2 gene occur in 20-30% of human breast, ovary, and gastric cancers. Overexpression or gene amplification has been associated with a proper disease prognosis. In Phase I, MAbs specific to the erbB-2 protein product were developed and their applications to diagnosis and therapy as potentially feasible was demonstrated. The results also indicate that anti-erbB-2 MAbs can inhibit the growth of experimental cells neoplastically transformed by erbB-2 overexpression. In Phase II study, these results will be extended by developing a quantitative immunohistochemical assay for erbB-2 expression. The prognostic significance of different levels of erbB-2 overexpression can then be determined. Further, it is proposed to examine if the growth of human tumor cells (that overexpress erbB-2) can be inhibited in culture and in nude mouse xenografts. Evidence of antibody mediated inhibition of growth will be examined in the context of the effects of chemotherapeutic agents on tumor cell growth. In order to support the above goals and to obtain optimal antibody reagents for each application, the investigators will continue to isolate additional monoclonal anti-erbB-2 antibodies and characterize their building epitopes.
| Kasprzyk, P G; Song, S U; Di Fiore, P P et al. (1992) Therapy of an animal model of human gastric cancer using a combination of anti-erbB-2 monoclonal antibodies. Cancer Res 52:2771-6 |
