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Article type: Research Article
Authors: Penichet, Manuel L.a | Dela Cruz, Jay S.a | Shin, Seung-Uonb | Morrison, Sherie L.a; *
Affiliations: [a] Department of Microbiology and Molecular Genetics, and The Molecular Biology Institute, University of California, Los Angeles, 405 Hilgard Avenue, Los Angeles, CA 90095-1489, USA | [b] Institute of Environment and Life Science, The Hallym Academy of Sciences, Hallym University, Chunchon, Kangwon-Do, Korea
Correspondence: [*] Corresponding author: Dr. Sherie L. Morrison, Department of Microbiology and Molecular Genetics, University of California, Los Angeles, 405 Hilgard Avenue, Los Angeles, CA 90095-1489, USA. Tel.: +1 310 206 5124; Fax: +1 310 206 5231; E-mail: [email protected].
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.
Keywords: antibodies, Cytokines, Immunotherapy, Cytotoxicity, Antibody Fusion Protein
DOI: 10.3233/HAB-2000-10107
Journal: Human Antibodies, vol. 10, no. 1, pp. 43-49, 2001
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