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Conjugation of interferon alpha to a humanized monoclonal antibody (HuBrE-3vl) enhances the selective localization and antitumor effects of interferon in breast cancer xenografts

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Abstract

Human mammary carcinoma xenografts (MCF-7) growing in nude mice were treated with natural interferon α (n-IFN-α) alone or conjugated to a humanized monoclonal antibody (MoAb) anti-breast mucin (HuBrE-3vl) or to irrelevant human IgG1κ. The IFN and the conjugates were administered as 20 intra-lesional (i.l.) injections to 1 of 2 xenografts in each mouse, or i.p. The growth inhibitory effects of HuBrE-3vl/nIFN-α were significantly greater than those of nIFN-α used as a single agent or conjugated to HuIgG1κ. These effects occurred locally in the tumors receiving i.l. injections and systemically, although to a slightly lesser extent, in the noninjected tumors of mice treated i.l. and in the xenografts of mice treated i.p. Biodistribution studies showed that the uptake of 125I-HuBrE-3vl/nIFN-α by the tumors 24 hours after i.l. or s.c. injection was greater than that of 125I-HuIgG1κ/nIFN-α,125 I-nIFN-α alone, or by normal tissues, documenting a tumor targeting effect and favorable tumor:normal tissues (T:NT) ratios. The targeting effects and the resulting tumor growth inhibition were favored by the IFN-mediated up-regulation of the HuBrE-3vl reactive antigen, which was more prominent after 3 weeks of treatment with HuBrE-3vl/nIFN-α. These results were superior to those we obtained previously with nIFN-α conjugated to another MoAb of the same group (Mc5). These studies point out the potential usefulness of HuBrE-3vl/nIFN-α for the local and systemic treatment of breast cancer lesions by providing a means of delivering high doses of IFN to the tumors while minimizing the amount of IFN binding to normal tissues.

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Authors
  1. L. Ozzello
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  2. E.W. Blank
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  3. C.M. De Rosa
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  4. R.L. Ceriani
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  5. H. Tölö
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  6. H-L Kauppinen
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  7. K. Cantell
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Ozzello, L., Blank, E., De Rosa, C. et al. Conjugation of interferon alpha to a humanized monoclonal antibody (HuBrE-3vl) enhances the selective localization and antitumor effects of interferon in breast cancer xenografts. Breast Cancer Res Treat 48, 135–147 (1998). https://doi.org/10.1023/A:1005934621940

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  • DOI: https://doi.org/10.1023/A:1005934621940

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