Monoclonal antibodies in cancer detection and therapy

Abstract

Anticancer antibodies have had a long history in the management of cancer, with major applications having been shown in the immunohistochemistry and immunoassay of tumor-associated antigen markers. With the advent of hybridoma-derived monoclonal antibodies, attempts to use these more reproducible reagents in vivo for cancer detection and therapy have intensified. Radiolabeled monoclonal antibodies appear to be gaining a role in the management of cancer by means of imaging methods to detect sites of increased radioactivity, and several products have been developed and tested clinically. In the area of radioimmunotherapy, a number of problems still need to be solved, including low tumor uptake of the radioimmunoconjugate, dose-limiting myelotoxicity, and the induction of an immune response to repeated doses of murine (foreign) immunoglobulins. Similar problems exist for toxin and drug immunoconjugates, but these also fail to benefit from the "bystander" effect of the ionizing radiation delivered with radioimmunoconjugates, and plant and bacterial toxin molecules appear to have additional immunogenicity that restricts repeated injections. Despite these limitations, recombinant engineering and other chemical approaches are making progress in developing second-generation immunoconjugates that may be more efficacious and less immunogenic as cancer-selective therapeutics. Although nonconjugated, "naked", murine monoclonal antibodies have shown limited success in the therapy of human neoplasms, human and "humanized" forms may be more effective, particularly in lymphatic tumors. Some evidence also suggests that anti-idiotype antibodies (antiantibodies) may serve as surrogate antigens in cancer vaccines. Thus, a number of promising immunologic approaches for cancer diagnosis, detection, and therapy have made important progress in recent years.