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The use of natural interferon alpha conjugated to a monoclonal antibody anti mammary epithelial mucin (Mc5) for the treatment of human breast cancer xenografts
Authors:L Ozzello  CM De Rosa  EW Blank  K Cantell  RL Ceriani  DV Habif Sr
Affiliation:(1) The Arthur Purdy Stout Laboratory of Surgical Pathology, Columbia University, New York, NY, USA;(2) Department of Surgery, Columbia University, New York, NY, USA;(3) The Cancer Research Fund of Contra Costa, Walnut Creek, CA, USA;(4) The National Public Health Institute, Helsinki, Finland;(5) Division of Surgical Pathology, Columbia-Presbyterian Medical Center, 630 West 168th Street, 10032 New York, New York, USA
Abstract:Summary An immunoconjugate composed of natural interferon agr (nIFNagr) bound in a noncleavable fashion to a monoclonal antibody (MoAb) recognizing a breast epithelial membrane mucin (Mc5) was used to treat xenografts of a human mammary carcinoma cell line (MCF-7) growing in nude mice. The immunoconjugate (nIFNagr/Mc5) was administered as 20 intralesional (i.l.) injections to 1 of 2 xenografts in each animal. It was found that nIFNagr/Mc5 produced a significant enhancement of the growth inhibitory actions of nIFNagr on the injected tumors. Further enhancement was obtained when nIFNgamma or nIFNgamma together with Mc5 (at a dose 10 times larger than that present in nIFNagr/Mc5) were added to the immunoconjugate. Biodistribution experiments showed that the uptake of125I-nIFNagr/Mc5 by the tumors was greater and its elimination slower than for125I-nIFNagr alone or conjugated to irrelevant mouse IgG1. In addition, the immunoconjugate up-regulated the antigenic expression of a breast epithelial membrane mucin by the carcinoma cells, an up-regulation which was not significantly different from that produced by nIFNagr alone. The contralateral noninjected tumors exposed to systemic levels of the immunoconjugate showed an enhancement of antitumor effects, but to a lesser extent than the injected tumors. These findings suggest that the enhancement of the growth inhibitory action of the immunoconjugate was related to the specific binding of Mc5 which targeted the IFN to the carcinoma cells and impeded its elimination. 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 study point out the feasibility and potential usefulness of IFN treatment by means of immunoconjugates as well as the worth of pursuing and improving this form of therapy.
Keywords:immunotherapy  breast carcinoma  interferon alpha  monoclonal antibodies  immunoconjugates
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