Suppression of human melanoma tumor growth in SCID mice by a human high molecular weight-melanoma associated antigen (HMW-MAA) specific monoclonal antibody.

Abstract

The lack of efficacy of available therapies for the treatment of malignant melanoma has emphasized the need to develop novel therapeutic strategies to prevent melanoma growth. We have tested whether the anti-HMW-MAA mAb 225.28S is able to inhibit human melanoma tumor growth in SCID mice because in vitro data suggested that this antigen plays a role in spreading, migration and invasion of melanoma cells. Tumors were established by subcutaneous injection of the human melanoma cell line 518A2 into SCID mice. When tumors reached a size of 5 mm, the mAb 225.28S was administered intravenously 4 times in 3 day intervals at 100 microg/injection. Within 14 days after the first administration of the mAb 225.28S, tumor growth was reduced by 52% as compared to control mice. Three hundred and seven genes of >20,000 genes contained on the GeneChip were changed in their expression level at least 2-fold after administration of the mAb 225.28S. The encoded proteins were mostly components or modifiers of the extracellular matrix, tumor suppressors, and melanogenesis associated proteins. Surprisingly, the administration of the control mAb that did not lead to a significant tumor growth inhibition in vivo resulted in the modulation of two-thirds of these genes. This is the first report of suppression of human melanoma tumor growth in SCID mice by the mAb 225.28S. Our results suggest that anti-HMW-MAA mAbs may represent useful reagents to apply passive immunotherapy to patients with malignant melanoma.

• Authors: Christine Hafner, Heimo Breiteneder, Soldano Ferrone, Christiane Thallinger, Stefan Wagner, Wolfgang M Schmidt, Joanna Jasinska, Michael Kundi, Klaus Wolff, Christoph C Zielinski, Otto Scheiner, Ursula Wiedermann, Hubert Pehamberger
• Journal: International journal of cancer (Int J Cancer) Vol. 114 Issue 3 Pg. 426-32 (Apr 10 2005) ISSN: 0020-7136 [Print] United States
• PMID: 15578703 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2004 Wiley-Liss, Inc.

Chemical References

• Antibodies, Monoclonal
• Antigens, Neoplasm
• Antigens, Surface
• Melanoma-Specific Antigens
• Neoplasm Proteins

Topics

• Animals
• Antibodies, Monoclonal (administration & dosage, immunology)
• Antigens, Neoplasm
• Antigens, Surface
• Cell Proliferation
• Disease Progression
• Female
• Gene Expression Profiling
• Genes, Tumor Suppressor
• Humans
• Immunization, Passive
• Infusions, Intravenous
• Melanoma (pathology)
• Melanoma-Specific Antigens
• Mice
• Mice, SCID
• Molecular Weight
• Neoplasm Proteins (immunology)
• Oligonucleotide Array Sequence Analysis
• Skin Neoplasms (pathology)
• Transplantation, Heterologous