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Tumor Growth Modulation by a Monoclonal Antibody to the Epidermal Growth Factor Receptor: Immunologically Mediated and Effector Cell-independent Effects¹

The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104 [U. R., M. H., D. H., C. M., Z. S., H. Z.], and Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104 [B. A., M. V.]

A monoclonal antibody of IgG2a isotype (425) is described that reacts with the epidermal growth factor receptor on human cells of different tissue origins. Monoclonal antibody 425 mediates tumor cytotoxicity in vitro using mouse and human effector cells and suppresses in vivo tumor cell growth of epidermoid (A 431) and colorectal (SW 948) carcinoma-derived cell lines. The tumoricidal effects in vitro are proportional to the antigen density on target cells. At concentrations higher than 1 nM, monoclonal antibody 425 inhibits growth of epidermal growth factor receptor-bearing A 431 cells, showing an epidermal growth factor-like agonist activity on the growth properties of these cells. A 431 cultures grown in the presence of growth-inhibiting doses of antibody or epidermal growth factor reveal a clear decrease of the relative number of cells in S phase. Additionally, cells treated with the antibody show a decrease of G₂-M-phase cells in some, but not all, cultures tested.

¹ These studies were supported by grants from the NIH, CA-25874, CA-28770, and CA-20815; a grant from the American Cancer Society, IM-402; and a grant from Deutsche Forschungsgemeinschaft, Ro 619.

² To whom requests for reprints should be addressed.

Received 12/19/86. Revised 4/16/87. Accepted 4/22/87.

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