A recombinant IgG3-(IL-2) fusion protein for the treatment of human HER2/neu expressing tumors.
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.
Penichet
M L
ML
Department of Microbiology and Molecular Genetics, and the Molecular Biology Institute, University of Califorina, Los Angeles, 405 Hilgard Avenue, Los Angeles, CA 90095-1489, USA.
Dela Cruz
J S
JS
Shin
S U
SU
Morrison
S L
SL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002460:Cell Line; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007376:Interleukin-2 / Q000235:genetics / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000628:therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D016756:Immunoglobulins, Intravenous; D007376:Interleukin-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D000068878:Trastuzumab