Tumor antigen heterogeneity may at times impact on monoclonal antibody (MAb) targeting, thereby compromising its overall effects as an immunodiagnostic and/or immunotherapeutic agent. This area of research involves the study of cytokines which up-regulate human tumor antigen expression. We have reported that the recombinant interferons can selectively enhance the expression of carcinoembryonic antigen (CEA), tumor-associated glycoprotein-72 (TAG-72) and a potentially novel Mr 110,000 antigen in a variety of human carcinomas. In a preliminary study, interleukin-6 treatment of human colon carcinoma cells was shown to also augment the level of expression of CEA and class l HLA. Interferon-gamma (IFN-gamma), in particular, substantially increases TAG-72 and CEA expression in human tumor xenografts leading to an increased tumor MAb localization. The ability of IFN-gamma to enhance MAb targeting to the tumor site provided a significant therapeutic advantage over the MAb administration alone. Those preclinical findings provided the rationale to investigate the ability of interferon to augment human tumor antigen expression in a clinical setting. Patients diagnosed with either ovarian or gastrointestinal carcinoma with secondary ascites were given weekly intraperitoneal doses of IFN-gamma (0.1 to 100 MU). Analyses of TAG-72 and CEA expression on isolated malignant ascites cells showed a dramatic increase in the expression of both tumor antigens as a result of IFN-gamma treatment. In some cases, IFN-gamma increased the percentage of tumor cells expressing either TAG-72 or CEA from 10% to 90% and those increases were observed at low IFN-gamma doses (ie, 0.1-1.0 MU) which were well tolerated by all patients. Thus, both experimental and early clinical results provide substantial support for the use of a cytokine as an adjuvant to enhance MAb localization to human carcinoma cell populations. Those changes may substantially improve MAb-based strategies designed for the diagnosis and treatment of human cancer.
