DEVELOPMENT OF A CAR NK CELL AGAINST ACUTE MYELOID LEUKEMIA DERIVED FROM UMBILICAL CORD BLOOD

• Grant number: 24/08168-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2025
• End date: February 29, 2028
• Field of knowledge: Biological Sciences - Immunology - Immunogenetics
• Principal Investigator: Nelson Hamerschlak
• Grantee: Érica Kássia Sousa Vidal
• Host Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil

Abstract

Immunotherapies using chimeric antigen receptor (CAR) anti-CD19 T cells have demonstrated surprising clinical efficacy against B-cell malignancies. However, the treatment of relapsed and refractory (R/R) acute myeloid leukemia (AML) has low cure rates. Despite the encouraging results with CAR-T therapy, the number of patients who relapse after treatment is worrying, with antigen loss being a mechanism described for treatment failure. To overcome antigen loss, CARs targeting multiple antigens are being explored. In addition, the study of new targets against myeloid leukemia cells is essential to avoid cytotoxicity outside the tumor. Additionally, CAR-T cells can induce graft-versus-host disease (GVHD). To overcome these limitations, the use of NK cells is being explored. NK cells are considered safer, as they usually do not cause GVHD, cytokine release syndrome or neurotoxicity, and can be used allogeneically. Umbilical cord blood (UCB) offers an attractive source of NK cells for use in adoptive immunotherapy. The main objective of this project is to modify NK cells from UCB to express bispecific CARs against acute myeloid leukemia. In this sense, NK cells will be transduced using lentiviral vectors and after expansion, we will evaluate the functionality of CAR-NK through in vitro and in vivo assays. The results of this project will contribute to the development of a new national treatment alternative for patients with R/R AML.