Synthetic nanobody platform implementation for antitumor immunotherapy solutions

• Grant number: 25/17890-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2025
• End date: November 30, 2028
• Field of knowledge: Health Sciences - Collective Health - Public Health
• Principal Investigator: Daniela Luz Hessel da Cunha
• Grantee: Melissa Arruda Vieira
• Host Institution: Instituto Butantan. São Paulo , SP, Brazil
• Associated research grant: 24/21826-9 - Development and implementation of platforms to produce nanobodies and sybodies for use in antitumor immunotherapy., AP.R

Abstract

Recent advances in biotechnology have driven the use of biopharmaceuticals in the treatment of chronic, infectious, and autoimmune diseases, with monoclonal antibodies widely used in targeted therapies, immunotherapy, and diagnostics. In Brazil, however, this market remains heavily dependent on imports, which significantly increases treatment costs, compromises national autonomy in healthcare, and limits the population's access to highly complex therapies. Given this scenario, the development of domestic platforms to produce bioactive molecules with greater technical and economic viability is strategic. Synthetic nanobodies, fragments derived from the variable heavy chain (VHH) domain of antibodies naturally present in camelids, have been consolidating as a promising alternative. With their compact structure, high stability, and ability to recognize cryptic or difficult-to-access epitopes, nanobodies can be efficiently expressed in bacterial systems, reducing costs and favoring industrial scalability. This project proposes the establishment of a national platform of synthetic nanobodies from high-diversity libraries to select ligands by phage display based on their target affinity. The initial target will be the TIM-3 receptor, an emerging checkpoint in cancer immunotherapy due to its role in T lymphocyte exhaustion and potential to restore the antitumor immune response. Once established, this platform can be easily repurposed for the development of synthetic nanobodies against various therapeutic targets, including toxins, tumor surface proteins, immune receptors, and clinical biomarkers, in addition to enabling applications in advanced therapies, such as CAR-T cells. Thus, in addition to fostering scientific and technological self-sufficiency, the development of this project represents a strategic initiative capable of reducing dependence on imports, expanding access to innovative treatments, and positioning the country more competitively in the biotechnology landscape.