Investigation of the effect promoted by MHC class II expressing cells on the differentiation of iPSC to T CD4+ lymphocytes

• Grant number: 24/00409-0
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: June 01, 2024
• End date: November 30, 2024
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Jose Alexandre Marzagão Barbuto
• Grantee: Luana Correia Croda Catharino
• Supervisor: George Q Daley
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Boston Children's Hospital, United States
• Associated to the scholarship: 22/11928-3 - Evaluation of the effect of the co-culture with dendritic cells in the phenotype and function of CAR-T cells derived from iPSC, BP.MS

Abstract

Among immunotherapies, the CAR-T cell therapy has been standing out in the past few years, given the promising results obtained for hematologic malignancies. The CAR-T cell products currently approved for clinical use are obtained from autologous T cell sources. However, the production of autologous CAR-T cells faces many manufacturing difficulties, such as the extensive production time, and the dysfunctional state and low numbers of T cells obtained from the patients. Thus, the use of off-the-shelf allogeneic sources, such as human iPSCs (Induced Pluripotent Stem Cells), could overcome these aspects. For the iPSCs differentiation to T cells, various methodologies have been described in the literature. However, limitations such as the need to use murine feeder-cells and the almost exclusive generation of T CD8+ cells restrict the future translational potential and possible long-term efficacy of these approaches. Therefore, this project proposes to use a stroma-free differentiation methodology to evaluate if the co-culture of iPSC-derived T lymphocytes with MHC class II expressing cells enables the generation of T CD4+ cells. The collaboration with Professor Daley's group will provide training to the student in iPSC differentiation to T lymphocytes and will allow the apprenticeship of new methodologies, such as the T lymphocytes CAR transduction using lentiviral vectors. Moreover, this project will also establish a new partnership with an international group which is a reference in stem cell research and that has similar ultimate goals as ours.