Modulation of antigen expression in human tumor cell populations

Monoclonal antibodies present new advantages to the cancer researcher for the detection and treatment of human carcinomas, melanomas, leukemias, and lymphomas. However, the overall effectiveness of monoclonal antibodies when used in detection or therapeutic modalities will undoubtedly be somewhat limited by the characteristics of the defined tumor antigens. We have shown that the pleiotropic genotypes of the human tumor cells have resulted in the evolution of heterogeneous cell populations with respect to antigen expression. Furthermore, the cell cycle dependence and the influence of the cell microenvironment have been shown to contribute to the quantitative, if not the qualitative, heterogeneity in antigen expression found on human tumor cells. As a result, when developing approaches for monoclonal antibody use, particularly in tumor therapy, one may need to consider combination therapy that includes a "cocktail" of monoclonal antibodies or the exogenous administration of a compound which will augment the binding of the monoclonal antibody to the tumor cell through the selective enhancement of the expression of cell surface tumor antigens. We have shown that in an in vitro experimental model recombinant interferon can render a human tumor cell population more homogeneous for the expression of a particular tumor antigen and thus enhance the localization of a monoclonal antibody to the tumor cell surface. Considerably more research needs to be done to determine whether such biological response modifiers or other immunomodulatory compounds can be effective when used in conjunction with monoclonal antibodies to optimize the detection and treatment of human carcinoma.