Our long range objective is to use monoclonal antibodies, which react with receptors for growth factors and hormones on the surfaces of human tumor cells, to prevent the proliferation of these cells in patients with cancer and to explore mechanisms by which binding of ligands to receptors results in altered proliferation. We have clearly demonstrated that anti-EGF receptor antibodies can inhibit proliferation to certain receptor- bearing malignant cells, both in culture and in xenografts. Because our anti-receptor antibodies are specific for the human EGF receptor, and do not cross react with the murine receptor, our previous studies have not enabled us to evaluate potential toxicity to the many normal tissues which bear receptors for EGF: in addition, they involve investigations of antitumor activity in an artificial hetero-transplant system. The present application focuses upon preclinical studies with an antibody (or antibodies) against the murine EGF receptor. We plan to determine whether anti-EGF receptor antibodies can be safely administered in vivo, and to explore their potential as antitumor agents with an experimental model which has similarity to naturally ocurring human cancer.
The Specific Aims of this proposal are as follows: 1) To determine whether single or multiple treatments with monoclonal antibodies against the EGF receptor result in either acute or prolonged toxicity to normal tissues. 2) To examine the antitumor activity of anti-EGF receptor antibodies against the spontaneous CD8F1 mammary carcinoma, and to determine the optimal schedule of antibody administration. 3) To explore treatment of the CD8F1 carcinoma with a combination of antireceptor antibody plus a corticosteroid. 4) To explore treatment of the CD8F1 carcinoma with a combination of antireceptor monoclonal antibody plus chemotherapy.
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