In silico analysis of endogenous retroviruses antigen expression in melanoma

• Grant number: 23/06627-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2023
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Luciana Rodrigues Carvalho Barros
• Grantee: Lucas Bicev Alencar
• Host Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Melanoma is a malignancy associated with melanocytes, and it is more commonly found on the skin. Around 325,000 new cases with an estimated 57,000 deaths occurred worldwide in 2020. The treatment for melanoma is based on chemotherapy with dacarbazine and BRAF and MEK inhibitors, because approximately half of the patients have mutations in the BRAF gene and one-fourth in NRAS. The importance of the immune system in this tumor is evident by the success of immunological checkpoint inhibitors such as ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-L1) therapy. In Brazil, the use of these medications was approved by ANVISA, but due to their high cost, they are not widely used for patients. In addition to mutations, neoplastic cells exhibit a global demethylation process that results in the expression of genes that are normally silenced, such as endogenous retrovirus and retrotransposon genes. When expressed, these genes could generate viral proteins that would be processed and presented to the immune system via MHC class I, unleashing a cytolytic response against tumor cells. In this project, we propose designing a vaccine for melanoma skin cancer based on the mRNA sequences of endogenous retroelements as a low-cost preventive and therapeutic strategy with broad application in the Sistema Único de Saúde (SUS). This approach could be used for other tumors in the future. At the end of the project, we aim to have a library of peptides with potential to be validated in future in vitro and in vivo, including murine, studies as proof of concept.