The ability to effectively target radionuclide conjugated monoclonal antibodies (MAb) to human tumor lesions depends, in part, on the degree to which the tumor cell population expresses the reactive carcinoma-associated antigens. Studies have shown that human tumor cells can intrinsically modulate their antigenic phenotype in response to cell-cycle kinetics, clonal variability, cell-to-cell interactions and other cellular factors. The resultant variability in the antigenic phenotype contribute to the antigenic heterogeneity present for most tumor antigens. We have established that certain biological response modifiers, specificaly human recombinant interferons, can upregulate some MAb-defined tumor antigens as well as induce the expression of class I and class II major histocompatibility antigens. Utilizing primarily human breast and colorectal tumor cell lines, recombinant leukocyte (clone A), the serine-substituted recombinant beta and recombinant gamma interferon have been shown to increase CEA and TAG-72 expression. Subsequent studies have also shown that the in vivo administration of the recombinant leukocyte (clone A) interferon can effectively increase CEA and the B6.2 reactive 90KD antigen in human extracts. In addition, the interferon increased in the MAb defined tumor antigens was also accompanied with an enhanced targeting of the radioconjugated MAb. These experimental studies clearly indicate that the antigenic phenotype of a human tumor cell population can be significantly altered following the administration of a recombinant human interferon. This effective activity of these biological response modifiers may be utilized as adjuvants in a clinical setting for the detection and/or therapy of occult lesions by conjugated MAbs.
