Experimental data have shown that recombinant human interferons can increase the level of expression of human tumor-associated antigens. Using a large number of colorectal carcinoma cell lines, both Type I (i.e., IFN-alpha and IFN-beta) and Type II (i.e., IFN-gamma) can enhance the cell surface expression level of CEA and related antigens as measured by monoclonal antibody binding. Complementary DNA probes of CEA and related antigens revealed that the increase was a result of alterations at the transcriptional and/or post-transcriptional level, not changes in the methylated state of the CEA gene(s). The level of expression of another human tumor antigen, tumor-associated glycoprotein-72 (TAG-72), was also found to be regulated by interferon. TAG-72, a high molecular weight mucin, is not found constitutively expressed on most adherent human carcinoma cell lines and, furthermore, its expression cannot be de novo induced by interferon. Serous effusions isolated from patients diagnosed with adenocarcinomas were found to constitutively express TAG-72. We have isolated carcinoma cells from >100 serous effusions, incubated them in the presence of Type I and II interferon, and found that level of TAG-72 expression could be enhanced (i.e >50%) in >80% of the samples. As a result of the preclinical studies, a phase I clinical trial was designed to investigate whether IFN-gamma could augment tumor antigen expression in patients. Eight patients with adenocarcinoma and secondary ascites were given i.p. escalating doses (i.e., 0.1-100 MU) of IFN-gamma for eight weeks. Tumor cells isolated from the ascites of seven of the eight patients constitutively expressed TAG-72 as measured in immunocytochemistry and flow cytometry using B72.3. In all seven patients, i.p. administration of IFN-gamma resulted in a discernable increase in the level of B72.3 binding. The findings present the initial observation that recombinant human interferon may serve as an adjunct by enhancing cell surface tumor antigen expression, thereby augmenting the localization of a monoclonal antibody.
