Targeting melanoma cells with human high molecular weight-melanoma associated antigen-specific antibodies elicited by a peptide mimotope: functional effects.

Abstract

Human high molecular weight-melanoma associated Ag (HMW-MAA) mimics have been shown to elicit HMW-MAA-specific humoral immune responses that appear to be clinically beneficial. This finding has stimulated interest in characterizing the mechanism(s) underlying the ability of the elicited Abs to exert an anti-tumor effect. To address this question, in the present study, we have generated HMW-MAA-specific Abs by sequentially immunizing rabbits with the peptide P763.74, which mimics the HMW-MAA determinant recognized by mAb 763.74, and with HMW-MAA(+) melanoma cells. HMW-MAA-specific Abs isolated from immunized rabbits mediated cell-dependent cytotoxicity but did not mediate complement-dependent cytotoxicity of HMW-MAA(+) melanoma cells. These Abs also effectively inhibited spreading, migration and Matrigel invasion of HMW-MAA(+) melanoma cells. Besides contributing to our understanding of the role of HMW-MAA in the biology of melanoma cells, these results suggest that both immunological and nonimmunological mechanisms underlie the beneficial clinical effects associated with the induction of HMW-MAA-specific Abs in melanoma patients immunized with a HMW-MAA mimic.

• Authors: Wei Luo, Eric Ko, Jeff Chi-feng Hsu, Xinhui Wang, Soldano Ferrone
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 176 Issue 10 Pg. 6046-54 (May 15 2006) ISSN: 0022-1767 [Print] United States
• PMID: 16670313 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neoplasm
• Antigens, Neoplasm
• Cancer Vaccines
• Drug Combinations
• Epitopes
• HMW-MAA
• Immunoglobulin G
• Laminin
• Peptides
• Proteoglycans
• matrigel
• Collagen
• Complement System Proteins

Topics

• Animals
• Antibodies, Neoplasm (biosynthesis, toxicity)
• Antibody Specificity
• Antibody-Dependent Cell Cytotoxicity (immunology)
• Antigens, Neoplasm (administration & dosage, immunology)
• Binding Sites, Antibody
• Binding, Competitive
• Cancer Vaccines (administration & dosage, immunology)
• Cell Line, Tumor
• Cell Movement (immunology)
• Collagen
• Complement System Proteins (physiology)
• Cytotoxicity, Immunologic
• Drug Combinations
• Epitopes (immunology)
• Humans
• Immunoglobulin G (toxicity)
• Laminin
• Melanoma (immunology, pathology)
• Molecular Mimicry (immunology)
• Peptides (administration & dosage, immunology)
• Proteoglycans
• Rabbits