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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CB009009-12
Application #
3774354
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Division of Cancer Biology and Diagnosis
Department
Type
DUNS #
City
State
Country
United States
Zip Code