Identification of the epitope recognized by anti-anti-Id mAb 5.G8

• Grant number: 11/22911-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2012
• End date: December 31, 2012
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Jane Zveiter de Moraes
• Grantee: Tábata de Almeida da Silva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Melanoma is the leading fatal illness arising from the skin. Currently, the conventional therapeutic modalities used for melanoma have not improved the survival of patients. Given that, immune therapies are being increasingly investigated. Studies on the molecular level show that changes in the expression pattern of gangliosides on the cell surface occur during the process of malignant transformation of melanocytes. The ganglioside GD3 is among the ones that are hyper-expressed and has been considered an important marker of human melanoma. However, immunization with GD3 leads to a short immune response, consisting of IgM antibodies mainly. It was shown that the anti-GD3 monoclonal antibody (mAb) R24, when administered intravenously, promoted regression of metastatic melanoma in patients by altering cell morphology and causing tumor growth inhibition. MAb R24, however, is a toxic antibody that limits its therapeutic application. To get around these problems, we proposed the use of the idiotype network approach. Through this strategy, we obtained the anti-anti-idiotype (Id) mAb 5.G8 (AB3) that was shown to recognize human melanoma cell lines in vitro, promoting antibody-dependent cytotoxicity (ADCC), complement fixation, and specific binding to enriched fractions of lipids extracted from human melanoma cells. In addition, mAb 5.G8 inhibits tumor growth in vivo. To be considered an alternative to mAb R24, mAb 5.G8 must be better characterized. This work aims to identify the epitope recognized by mAb anti-id 5.G8.). (AU)