Engineering and production of recombinant proteins for antitumor immunomodulation using a baculoviral expression system.

• Grant number: 24/09553-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2024
• End date: September 30, 2025
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Marcio Chaim Bajgelman
• Grantee: Iara Vilarino Chartouni
• 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 through direct action on tumor cells or by modulating immune system cells to overcome immunosuppressive mechanisms that can antagonize the antitumor response. In this regard, monoclonal antibodies have been extensively investigated. Examples include the use of ADCC-mediating antibodies, such as trastuzumab, which recognizes the her-2 receptor constitutively expressed in breast tumors, or immune checkpoint inhibitor antibodies such as nivolumab, which blocks the PD1/PDL1 pathway. In addition to blocking surface receptors on immune system cells, other strategies target signaling mediated by agonist molecules; however, there are reports of toxicity associated with their systemic use due to the non-specific action of agonist antibodies in non-tumor sites. Therefore, this project aims to develop a recombinant chimeric protein that features a tropism-directing portion for prostate cancer, fused to a murine 4-1BB costimulatory motif. This strategy could enable the future use of agonist molecules systemically, directing them to the tumor site and minimizing adverse effects.