THE USE OF NATURAL INTERFERON-ALPHA CONJUGATED TO A MONOCLONAL-ANTIBODY ANTIMAMMARY EPITHELIAL MUCIN (MC5) FOR THE TREATMENT OF HUMAN BREAST-CANCER XENOGRAFTS

An immunoconjugate composed of natural interferon alpha (nIFNalpha) bo und in a noncleavable fashion to a monoclonal antibody (MoAb) recogniz ing a breast epithelial membrane mucin (Mc5) was used to treat xenogra fts of a human mammary carcinoma cell line (MCF-7) growing in nude mic e. The immunoconjugate (nIFNalpha/Mc5) was administered as 20 intrales ional (i.l.) injections to 1 of 2 xenografts in each animal. It was fo und that nIFNalpha/Mc5 produced a significant enhancement of the growt h inhibitory actions of nIFNalpha on the injected tumors. Further enha ncement was obtained when nIFNgamma or nIFNgamma together with Mc5 (at a dose 10 times larger than that present in nIFNalpha/Mc5) were added to the immunoconjugate. Biodistribution experiments showed that the u ptake of I-125-nIFNalpha/Mc5 by the tumors was greater and its elimina tion slower than for I-125-nIFNalpha alone or conjugated to irrelevant mouse IgG1. In addition, the immunoconjugate up-regulated the antigen ic expression of a breast epithelial membrane mucin by the carcinoma c ells, an up-regulation which was not significantly different from that produced by nIFNalpha alone. The contralateral noninjected tumors exp osed to systemic levels of the immunoconjugate showed an enhancement o f antitumor effects, but to a lesser extent than the injected tumors. These findings suggest that the enhancement of the growth inhibitory a ction of the immunoconjugate was related to the specific binding of Mc 5 which targeted the IFN to the carcinoma cells and impeded its elimin ation. It is likely that the targeting was favored by the IFN-mediated up-regulation of antigenic expression by the carcinoma cells, thereby producing a cascade of interrelated effects. The results of this stud y point out the feasibility and potential usefulness of IFN treatment by means of immunoconjugates as well as the worth of pursuing and impr oving this form of therapy.