A novel nanobody-based TCR-like CAR-T therapy targeting PRAME for the treatment of acute myeloid leukemia

Chimeric antigen receptor (CAR) T-cell immunotherapy in acute myeloid leukemia (AML) remains challenging, primarily due to the lack of specific cell surface antigens that are highly expressed on leukemic blasts but largely absent on hematopoietic stem/progenitor cells and healthy tissues. TCR-like CAR-T therapy targeting intracellular antigens provides a novel strategy for the treatment of AML. In this study, we aimed to develop nanobodies targeting the intracellular antigen PRAME and to establish a novel nanobody-based TCR-like CAR-T cell therapy directed against the peptide-MHC complex PRAME425-433/HLA-A2.