Abstract
Anti-HER2/neu therapy of human HER2/neu expressing malignancies such as breast cancer has shown only partial success in clinical trials. To expand the clinical potential of this approach, we have genetically engineered an anti-HER2/neu human IgG3 fusion protein containing interleukin-2 (IL-2) fused at its carboxyl terminus. Anti-Her2/neu IgG3-(IL-2) retained antibody and cytokine related activity. Treatment of immunocompentent mice with this antibody fusion protein resulted in significant retardation in the subcutaneous (s.c.) growth of CT26-HER2/neu tumors suggesting that anti-HER2/neu IgG3-(IL-2) fusion protein will be useful in the treatment of HER2/neu expressing tumors. We also found that fusing IL-2 to human IgG3 results in a significant enhancement of the murine anti-human antibody (MAHA) response.
MeSH terms
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Animals
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Antibodies, Monoclonal / genetics
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal, Humanized
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Antibodies, Neoplasm / genetics
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Antibodies, Neoplasm / immunology
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Antibodies, Neoplasm / therapeutic use
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Antineoplastic Agents / therapeutic use*
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Cell Line
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Female
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Humans
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Immunoglobulin G / genetics
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Immunoglobulin G / immunology
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Immunoglobulin G / therapeutic use*
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Immunoglobulin Variable Region / genetics
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Immunoglobulin Variable Region / immunology
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Immunoglobulins, Intravenous / therapeutic use
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Interleukin-2 / genetics
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Interleukin-2 / therapeutic use*
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Mice
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Mice, Inbred BALB C
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Neoplasms, Experimental / therapy*
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Receptor, ErbB-2 / biosynthesis*
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Receptor, ErbB-2 / immunology
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Recombinant Fusion Proteins / therapeutic use
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Trastuzumab
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Antibodies, Neoplasm
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Antineoplastic Agents
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Immunoglobulin G
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Immunoglobulin Variable Region
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Immunoglobulins, Intravenous
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Interleukin-2
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Recombinant Fusion Proteins
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Receptor, ErbB-2
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Trastuzumab