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.

• Grant number: 25/00538-8
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: October 01, 2025
• End date: January 31, 2026
• Field of knowledge: Health Sciences - Collective Health - Public Health
• Principal Investigator: Daniela Luz Hessel da Cunha
• Grantee: Marielly Câmara Rocha
• Supervisor: Tobias Schatton
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: Brigham and Women's Hospital (BWH), United States
• Associated to the scholarship: 24/03401-0 - Development of the biosimilar Fab version of the monoclonal Nivolumab (anti-PD1) as an immunobiological tool for prospecting new antitumor strategies., BP.IC

Abstract

Despite advances in research, skin cancer remains the most common type of tumor in Brazil. Nivolumab, an anti-PD-1 monoclonal antibody, has shown success in the treatment of melanoma. This antibody blocks the immune checkpoint PD-1, a molecular receptor expressed by immune cells that when interacts with their ligands leads these cells to an exhaustion state, in which they present altered functional characteristics and become incapable of exerting cytotoxic and antitumor activities. The development of immune checkpoint inhibitors biosimilars whose production is fast and low cost proves to be an important immunotherapeutic strategy in developing countries, such as Brazil. In this scenario and, inserted in a context of improving public health and offering national biopharmaceuticals, this project aims to investigate, in melanoma models, the role of anti-PD-1 glycosylation (nivolumab) in PD-1 blockade using the non-glycosylated IgG and Fab versions, comparing with the original version of the drug. The evidence generated in this project can be a milestone for a more affordable production of antitumor mAbs, since non-glycosylated antibodies can be produced in microbial systems of bacteria, a simpler and more accessible recombinant production platform, Further democratizing access to these molecules so important in antitumor treatment. (AU)