Recombinant TIM-3FC obtainment as antigen for antibodies selection for anti-tumor therapy

• Grant number: 22/11876-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2022
• End date: November 30, 2023
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Daniela Luz Hessel da Cunha
• Grantee: Marielly Câmara Rocha
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Immune checkpoints are negative regulatory receptors expressed on immune cells. Under normal physiological conditions, its function is to act as a brake on the immune system, maintaining self-tolerance and preventing immunopathologies. However, these molecules also participate in immune escape mechanisms, causing dysfunction in T cell populations in a variety of diseases, including cancer. Among them, TIM-3 stands out for its involvement with changes in T cell functions in several tumors. Inhibition of the interaction of TIM3 with its ligands by therapeutic antibodies, such as LY3415244, LY3321367 and Sabatomimab, showed promising results as an antitumor agent in preclinical and early-stage clinical studies. However, despite significant advances in research, cancer still poses a threat to global health. Moreoverto date, the immune response of many patients to immunotherapy reaches a maximum of 40%. The recombinant antibodies development which synthesis and production is versatile and diversified, represents the possibility of obtaining new and differentiated molecules that act in the reversal of the condition of exhaustion of T cells and that can significantly increase the efficiency of immunotherapy. The presentation of quality antigens increases the chances of obtaining antibodies with high affinity and therapeutic potential. In this sense, the project's main objective is to clone the extracellular portion of TIM-3 for its expression fused to the FC portion of antibodies, which will facilitate the purification of this molecule in order to maintain its conformation, in addition to allowing its complete presentation. for the selection of recombinant antibodies by phage display, using a synthetic human antibody library. Such antibodies, after characterized, may be promising therapeutic tools in immunotherapy.