Active immunization whith derived peptídeo from matriptase

• Grant number: 23/07511-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2023
• End date: March 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Katiuchia Uzzun Sales
• Grantee: Luciano Renan da Silva Araújo
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Head and neck carcinoma (HNSCC) is a neoplasm with a high incidence rate and aggressiveness, however, the forms of treatment have little specificity, using the same chemotherapy agents for over 50 years. Matriptase is a type II transmembrane serine protease (TTSP), which plays a crucial role in maintaining the physiological functions of epithelial tissues. However, its expression is increased in malignant tumors of these tissues, with emphasis on HNSCC. Studies demonstrate that overexpression of matriptase is correlated with progression and advanced tumor stage, resulting from deregulation of its inhibitors, hepatocyte growth factor-1 and -2 (HAI-1 and HAI-2), or from its self-activation. Immunotherapies, in the treatment of cancer, are efficient, in this sense, the objective of this research project is to develop and test an active immunization methodology against the serine protease matriptase. Methodologically, subsequent immunizations, with peptide mimicking the serine protease domain of the enzyme, for a period of 15 weeks, will be combined with the application of DMBA (dimethylbenz(a)anthracene), an inducer of malignant epithelial lesions, in transgenic mice that overexpress matriptase.The search for new treatments is justified, given the clinical need for more specific therapeutic targets available to offer better quality of life to patients affected by this pathology. It is therefore expected that mimetic peptide immunization results in decreased activation of proteolytic pathways that depend on matriptase.