Generation of dendritic cells expressing CAR from induced pluripotent cells: an alternative treatment for cancer

• Grant number: 23/11172-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2024
• End date: August 31, 2027
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Rodrigo Nalio Ramos
• Grantee: Paula do Amaral Costa Ribeiro
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cell therapy is a branch of immunotherapy that has been growing in recent decades and shows to be a promising strategy to treat tumors. The fastest growing modality in recent years is therapy based on T cells expressing Chimeric Antigen Receptor (CAR-T). Six products of CAR-T have been approved by the FDA (Food and Drug Administration, USA), all for hematological tumors. Despite the success in hematological tumors, the same has not been reported in solid tumors. The tumor microenvironment is hostile and has physicochemical barriers that generate an immunosuppressive profile. In this context, other immune cells are being explored to receive CAR to increase the antitumor response in solid tumors. Dendritic cells (DC), despite being heterogeneous, are specialized in antigen presentation and stimulating the adaptive immune response, being good candidates to receive CARs. Among the subtypes, there are cDC1 and cDC3, which can, respectively, promote cross-presentation of antigens and induce a resident memory phenotype in antitumor CD8+ T lymphocytes. However, due to its scarcity in peripheral blood and its low proliferative potential, an "off-the-shelf" source is needed to enable its use in cell therapy. The use of induced pluripotent cells (iPSC) as a source of DCs can overcome these obstacles, as they have an indefinite potential for self-renewal and proliferation, in addition to being easily genetically modified. Therefore, our project aims to generate a platform to produce cDC1 and cDC3 cells expressing CAR from iPSC cells to develop a new strategy for cancer treatment.