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Isolation of anti-TIM-3 antibodies from combinatorial libraries expressed in the cytoplasm of Escherichia coli.

Grant number: 24/01723-0
Support Opportunities:Scholarships abroad - Research Internship - Doctorate (Direct)
Effective date (Start): June 01, 2024
Effective date (End): November 30, 2024
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:Daniela Luz Hessel da Cunha
Grantee:Gabriel Correia Lima
Supervisor: Matthew Delisa
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Research place: Cornell University, United States  
Associated to the scholarship:23/01816-6 - Phage display selection of non-glycosylated recombinant human antibodies against TIM-3, PD-1 and LAG-3 immune checkpoints, and their characterization as antitumor and antiviral therapeutic molecules, BP.DD

Abstract

This research focuses on immune checkpoints, crucial regulators of T lymphocyte activity. Immune checkpoint discovery began in the 1990s with proteins like PD-1 and CTLA-4. TIM-3 is also a checkpoint associated with tumor and virus evasion and its blockade by monoclonal antibodies has proved capable of being used as a target for anti-tumor therapies. Immunotherapy, utilizing monoclonal antibodies (mAb) to inhibit checkpoints, has revolutionized tumor treatment. Monoclonal antibodies (mAbs) are pivotal in biotechnology, especially in oncology. Our group at the Butantan Institute's Antibody Development Lab has made progress in antibody fragment development. However, transitioning these to IgG format can be complex and impact antigen interaction. A selection system utilizing IgG format is of great interest. This project aims to employ a genetic selection strategy in Eschericha coli (E. coli) for isolating full-length IgGs targeting TIM-3. The method leverages substrate proteins incorporating an antigen fused to chloramphenicol acetyltransferase (CAT). Using the genetically engineered E. coli strain SHuffle, high-level functional expression of cyclonals is achieved. In conclusion, this research proposal outlines a strategic approach to harness the potential of genetic selection in E. coli for the development of anti-TIM-3, full-length IgG antibodies, representing a promising avenue in the field of immunotherapy against immune checkpoints.

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