Construction and characterization of a 4-1BBL chimeric protein for antitumor immunomodulation

• Grant number: 22/08863-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2023
• End date: July 31, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Marcio Chaim Bajgelman
• Grantee: Daniele Enriquetto Mascarelli
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil

Abstract

Cancer immunotherapy is a strategy that aims to enhance the detection and elimination of tumor cells by modulating the balance between immunotolerance and immunosurveillance. In this sense, several approaches to strengthen the lymphocyte-mediated response have revolutionized clinical medicine, such as monoclonal antibodies, known as checkpoint inhibitors, which arebind to surface receptors on T cells, blocking immunosuppressive signaling, preventing lymphocyte anergy and promoting tumor elimination. In addition to this approach based on blocking immunosuppressive signaling, other strategies seek to induce agonist signaling, through costimulatory lymphocyte receptors. Molecules that promote tumor costimulation, such as members of the tumor necrosis factor family, are therefore promising for efficient tumor immunotherapy. In this project, our proposal is to develop a bifunctional chimeric protein that presentsa portion of the 4-1BB ligand fused to a second portion that binds to the PSMA receptor, found on the surface of PSMA positive prostate tumors. Thus, we will be able to modulate a co-stimulatory response, through the 4-1BBL portion, potentiating lymphocyte activity, in a targeted manner at the tumor site.