TUMOR-SPECIFIC IGE-MEDIATED INHIBITION OF HUMAN COLORECTAL-CARCINOMA XENOGRAFT GROWTH

Antibodies have found application in the diagnosis and therapy of canc er. These antitumor antibodies are confined to isotypes of IgG and lit tle is known of the potential usefulness of other classes of immunoglo bulin. In order to determine a possible antitumor effect of IgE antibo dy a tumor-specific mouse monoclonal IgE antibody was constructed. Thi s antibody was derived from the mouse monoclonal antibody 30.6 that de tects an antigenic determinant expressed on the surface of colorectal adenocarcinoma cells, including COLO 205. Mouse IgE 30.6 inhibited the growth of established COLO 205 tumor growing subcutaneously in scid m ice. This effect was transient with tumor growth returning to pretreat ment levels after 48 h. By contrast, a mouse IgG 30.6 and a chimeric h uman/mouse IgE 30.6 were without antirumor effect. This isotype-specif ic antirumor effect was not attributable to differences in antibody af finity, tumor Localization, or serum half-life as these were essential ly the same for all three isotypes of antibody. In addition, none of t he 30.6 monoclonal antibodies inhibited the growth of COLO 205 cells i n vitro. As little as 1 mu g per mouse of the tumor-specific mouse IgE antibody was sufficient to inhibit COLO 205 tumor growth, which is in contrast to previous results in which the comparatively weak antirumo r effect of a chimeric human/mouse IgG(1) required an optimum dose of 4 x 250 mu g per mouse. This antitumor effect of mouse IgE 30.6 was sp ecifically abrogated by prior administration of a nonspecific mouse Ig E. Given this potency, and the fact that mouse Fc epsilon RI binds mou se IgE, but not human IgE, a role for Fc epsilon receptor bearing effe ctor cells in the observed antirumor effect is discussed.