Establishment of a high-throughput CRISPR screenig platform for functional genomics studies and generation of new immunotherapies against colorectal tumors

• Grant number: 24/04112-2
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Start date: December 01, 2024
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Nerry Tatiana Cecilio
• Grantee: Nerry Tatiana Cecilio
• Company: EDITBIO BIOTECNOLOGIA LTDA
• CNAE: Pesquisa e desenvolvimento experimental em ciências físicas e naturais
• City: Ribeirão Preto
• Associated scholarship(s): 24/16900-5 - Establishment of a high-throughput CRISPR screening platform for functional genomics studies and the development of new immunotherapies against colorectal tumors, BP.PIPE; 24/18685-4 - Standardization of cell-based assays demonstrating the viability of the high-throughput CRISPR screening platform for functional genomics studies and the generation of new immunotherapies against colorectal tumors, BP.TT

Abstract

The global market for cell and gene therapy is on the rise, driven by advances in CAR-T and RNA vaccines. Brazil leads this market regionally, but technological studies are still limited, affecting the population's access to these innovative therapies. While CAR-T cells are effective in treating liquid tumors, their efficacy against solid tumors is restricted, prompting interest in other immune cells like macrophages due to their ability to infiltrate tumors and modulate the local immune response. However, macrophages can have pro- or antitumoral effects depending on the tumor microenvironment (TME). In the specific case of colorectal tumors, accumulating evidence shows that macrophage infiltration in the TME is closely related to the clinical prognosis of affected patients, suggesting that reeducation of these cells' polarization could facilitate antitumoral immunotherapy. Functional genomics studies are essential for this purpose. We propose establishing a platform enabling genomic screening using CRISPR-Cas9 to identify genes regulating macrophage activity associated with colorectal tumors, aiming to generate new and innovative oncological immunotherapies. Resources to be raised through PIPE phase I include investments in supplies, services, and human resources to test platform viability. The results obtained will allow us to develop new cellular therapies through macrophage gene editing, potentially treating metastatic or unresectable colorectal tumors and other solid tumor types in the future. These results will also be used as a marketing differentiator, attracting strategic partnerships with pharmaceutical and biotechnology industries and investors to expand operations and develop our products. Ultimately, these innovations have the potential to boost the national biotechnology sector, strengthening the economy and advancing science and public health in the country. (AU)