Abstract: Disclosed are methods and compositions for identifying malignant tumors that overexpress the c-erbB-2 oncogene. Assays useful for diagnosis and prognosis of neoplastic disease are provided which detect the external domain of c-erbB-2, the glycoprotein gp75 and quantitate the level of gp75 in the biological fluids of mammals carrying a tumor burden. Further disclosed are recombinant, synthetically and otherwise biologically produced novel proteins and polypeptides which are encoded by the external domain DNA sequence of the c-erbB-2 oncogene (the gp75 gene) or fragments thereof. Such gp75 proteins and polypeptides are useful as vaccines, therapeutically in the treatment of cancer either alone or in combination with chemotherapeutic agents. Also disclosed are antibodies to such gp75 proteins and polypeptides which are useful diagnostically and therapeutically. Still further disclosed are test kits embodying the assays of this invention.

Abstract: This invention is directed toward novel synergistic combinations of ligand-mimicking agents specific to the c-erbB-2 protein and anti-neoplastic drugs or agents, which can be used to treat a mammalian host, usually a human, suspected of having cancer or tumor cells by administering the combination in a therapeutically- or synergistically-effective amount. The drug combinations cytotoxic to tumor cells comprise an anti-neoplastic agent and a molecule, that is not conjugated to the anti-neoplastic agent, that binds the tumor cells and induces an increase in the phosphorylation of c-erbB-2 protein when placed in contact with the tumor cells. Alternatively, the drug combination cytotoxic to tumor cells may comprise an anti-neoplastic agent and a molecule, that is not conjugated to the anti-neoplastic agent, that binds the tumor cells and causes down modulation or internalization of c-erbB-2 protein. The anti-neoplastic drug is preferably an alkylating agent, most preferably cisplatin.