CAR-T Cells for Treating Acute Myeloid Leukemia

Acute myeloid leukemia (AML) remains a highly challenging disease to treat, largely due to the persistence of leukemic stem cells (LSCs). In Saudi Arabia, the burden is particularly high, with a large number of young AML patients disproportionately affected by an unfavorable disease course. These patients remain underserved, as efficacious therapies tailored to their needs have yet to be developed. Globally, no FDA-approved Chimeric Antigen Receptor (CAR) T-cell therapies currently exist for AML, leaving high-risk patients with few options when conventional treatments fail to induce durable remission.

Among potential targets, Interleukin-1 Receptor Accessory Protein (IL-1RAP) has emerged as a promising AML-specific antigen due to its selective expression on leukemic stem cells and blasts, with minimal presence on normal hematopoietic stem cells. Our results demonstrate that IL-1RAP CAR-T cells exhibit strong antigen-specific cytotoxicity against IL-1RAP-positive AML cell lines and primary patient samples, and effectively eradicate AML cells in the preclinical mouse model. These findings highlight the potential of IL-1RAP CAR-T cells as a novel immunotherapeutic strategy for AML.