Leukemia-associated antigen-specific T cells (LAA-T cells) (LAA-T cells)

Leukemia-associated antigen-specific T cells (LAA-T cells) are a specialized form of adoptive cellular immunotherapy designed to recognize and eliminate malignant cells in hematologic cancers. These cells are typically generated by expanding a patient's or donor's T cells ex vivo to target a panel of proteins that are highly expressed in leukemia but have limited expression in healthy tissues, such as Wilms Tumor 1 (WT1), PRAME, and Survivin (Lulla et al., 2021; PMID: 33171475). Unlike Chimeric Antigen Receptor (CAR) T cells, LAA-T cells utilize their endogenous T-cell receptors (TCRs) to identify intracellular antigens presented as peptides on Major Histocompatibility Complex (MHC) molecules (Weber et al., 2017; PMID: 28811303). This approach allows for the simultaneous targeting of multiple antigens, which helps prevent tumor escape through antigen loss and reduces the likelihood of off-target toxicity. These therapies are primarily being developed for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), often as a consolidation therapy to prevent relapse after hematopoietic stem cell transplantation (Marker Therapeutics, 2024). By providing a broad and durable immune response, LAA-T cells aim to improve long-term outcomes for patients with high-risk leukemias.

Other names

Multi-LAA-specific T cellsLeukemia-reactive T cellsMulti-antigen targeted T cellsLAA-specific cytotoxic T lymphocytes

LAA-specific T cells recognize leukemia-associated antigen peptides presented by MHC molecules on the surface of leukemic cells via their endogenous T-cell receptors (TCRs), leading to the activation of cytotoxic pathways, including the release of granzymes and perforin, which induce apoptosis in the target cells (Lulla et al., 2021; PMID: 33171475).