Development of the biosimilar Fab version of the monoclonal Nivolumab (anti-PD1) as an immunobiological tool for prospecting new antitumor strategies.

• Grant number: 24/03401-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2024
• End date: June 30, 2026
• Field of knowledge: Health Sciences - Collective Health - Public Health
• 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
• Associated research grant: 22/04560-0 - Platforms developing for obtaining and characterizing non-glycosylated recombinant antibodies against the TIM-3 immune checkpoint and evaluating the role of these antibodies in the reactivation of T lymphocytes in tumors, AP.R
• Associated scholarship(s): 25/00538-8 - Investigation of the impact of PD-1 blockade on the response to immunotherapy with the Fab and IgG non-glycosylated versions of the monoclonal antibody Nivolumab in melanoma models., BE.EP.IC

Abstract

Despite significant advances in research, cancer still represents a threat to global health. The chronicity of this disease and constant antigenic stimulation leads to the differentiation of CD8+ T cells into populations with altered effector functions, a unique epigenetic profile, and high levels of expression of multiple inhibitory receptors. Such negative regulatory receptors have the function of serving as brakes for the immune system, maintaining self-tolerance, and preventing tissue damage, being expressed in immune cells under normal physiological conditions. However, these molecules also participate in immune system escape mechanisms in the development of tumors. Therapies aimed at blocking these molecules are attractive in the treatment of different types of tumors. In this context, immunotherapy has emerged using monoclonal antibodies to block receptors such as PD-1, thereby restoring the ability of exhausted T cells to eliminate tumors and viruses. However, most of these commercial antibodies are produced in mammalian cells or hybridomas by pharmaceutical companies located outside of Latin America. Moreover, the microbial expression system in Escherichia coli proposes a faster and lower-cost alternative in the production of these molecules, being widely used in the production of recombinant proteins on a large scale. In this scenario and, within a context of improving public health and offering national biopharmaceuticals, the present project aims to develop the Fab biosimilar version of the monoclonal Nivolumab, a blocker of the PD-1 immune control receptor, based on microbial expression in E. coli, aiming to reduce costs and the national and Latin American market.