In Vitro Tests for the Development of an Anti-IL1RAP Chimeric Antigen Receptor (CAR) for the Treatment of Acute Myeloid Leukemia

• Grant number: 25/04084-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2025
• End date: June 30, 2027
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Lucila Nassif Kerbauy
• Grantee: Ingrid Ferreira de Souza
• Host Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). São Paulo , SP, Brazil

Abstract

Acute Myeloid Leukemia (AML) is an aggressive hematological neoplasm characterized by a failure in the differentiation of myeloid progenitor cells, resulting in disordered proliferation of immature cells. Commonly diagnosed in patients aged 60 and over, AML has an unfavorable prognosis, especially in relapsed or refractory cases. Standard therapy with aggressive chemotherapy has limited results, with high relapse rates and short overall survival. Thus, Chimeric Antigen Receptor-modified T-cell (CAR-T) therapies have shown great therapeutic potential in lymphoid leukemias and multiple myeloma, but their use in AML faces challenges due to the high genetic heterogeneity of the disease and the difficulty in identifying specific antigens. Strategies that incorporate specific modifications to the CAR construct, such as the addition of cytokines like IL-15 to potentiate the function of T cells, have shown promise in increasing the efficacy and durability of the therapeutic response. In this context, a promising target under study is the accessory protein IL1RAP (Interleukin-1 receptor accessory protein), which has high expression in myeloid leukemia cells and no significant expression in healthy hematopoietic cells. The aim of this project is to compare the efficacy of T cells modified with a second-generation CAR and a fourth-generation CAR containing IL-15, both targeting IL1RAP, and to evaluate their in vitro therapeutic potential against AML cells.