Evaluation of treatment of human malignant melanoma with humanized monoclonal antibodies to EFGR, HER-2 and rabbit polyclonal antibody to Dermcidin

• Grant number: 10/14839-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2010
• End date: November 30, 2012
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: José Ernesto Belizario
• Grantee: Beatriz Areias Sangiuliano
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The dermicidina (DCD) is a protein encoded by a gene located on loci 12q13.1 of chromossome 12 of primates and humans. The precursor of 11 kDa and their peptides are produced by cells of eccrine glands of the skin, melanocytes, neurons and epithelial cells of breast and placenta. Studies in our laboratory showed that the superexpression od DCD gene or stimulation of cells with recombinant DCD protein increase the proliferation and cell division and cell survival to oxidative stress in several cell types. In preliminary studies, we demonstrated that silencing of DCD by constitutive expression of RNA interference (RNAi) caused significant reduction in tumor formation by human malignant melanoma G-361 cells. Furthermore, we show that administration of weekly dose for 4 times, polyclonal antibodies produced in mouse, rabbit and goat specific to DCD inhibited G-361 tumor growth in immunodeficient mice. In this project we intend to continue the studies evaluating the therapeutic effects of polyclonal anti-DCD in the growth of G-361 cells in culture and immunodeficient animals. Considering, however, that DCD may exert its effects via modulation of the expression of EGFR/Erbbs family of receptors, we will assess the therapeutic effects, either alone or in combination, of the recombinant humanized monoclonal antibodies Nimotuzumabe / CIMAher and trastuzumab / herceptin, specific for the EGFR and HER-2, respectively, and anti-DCD.