Immunotoxins against solid tumors.

Abstract

Antibody-toxin conjugates, termed immunotoxins, are currently being evaluated as potential new anticancer agents. The monoclonal antibodies that recognize antigens on the surface of tumor cells should deliver the toxins or the catalytic subunits of toxins to cancer cells. The catalytically active parts of the immunotoxins have to reach the cell cytoplasm where they inhibit protein synthesis. Immunotoxins against various solid tumors, including breast carcinoma and ovarian carcinoma, have been developed. In vitro, the activity of immunotoxins is affected by the number of target antigens on the cell surface, the internalization of the immunotoxins, the kind of toxin, the class of the antibody, the kind of linkage, and by other factors. Several problems arise with in vivo administration of immunotoxins. The short serum half-life of immunotoxins, due to their rapid hepatic uptake, decreases the number of immunotoxin molecules that reach the solid tumor. This, together with low tumor penetration by immunotoxins, could lead to low anti-tumor activity. Heterogeneity of tumors, immunogenicity of immunotoxins, and cross-reactivity of immunotoxins with normal tissues are other factors that might limit the clinical use of immunotoxins. It should be possible, however, to overcome these problems using methods that are already available or have yet to be developed.