T-lymphocytes involved in anti-AML cytotoxic responses

T-lymphocytes involved in anti-AML cytotoxic responses are a specialized subset of immune effector cells, primarily CD8+ T cells, that mediate the graft-versus-leukemia effect and natural immunosurveillance against Acute Myeloid Leukemia (AML) (Noviello et al., 2019). These cells recognize leukemia-associated antigens (LAAs) such as Wilms Tumor 1 (WT1) or Proteinase 3 (PR3) through their T-cell receptors (TCRs) (Lichtenegger et al., 2017). In the AML microenvironment, these T cells often undergo functional exhaustion, characterized by the high expression of inhibitory checkpoints like PD-1, TIM-3, and LAG-3, which allows the leukemia to evade immune detection (Daver et al., 2019). Therapeutic interventions aim to reinvigorate or redirect these cells; for instance, bispecific T-cell engagers (BiTEs) like Vibecotamab link CD3 on T cells to CD123 on AML blasts to trigger MHC-independent cytotoxicity (Huybrechts et al., 2020). Additionally, Chimeric Antigen Receptor (CAR) T-cell therapies are being developed to engineer these lymphocytes to specifically target AML surface markers like CD33 (Richman et al., 2023). However, the clinical utility of these T-cell-based therapies is often limited by risks such as Cytokine Release Syndrome (CRS) and the lack of truly leukemia-specific antigens, leading to potential on-target, off-tumor toxicity against healthy hematopoietic stem cells (Knaus et al., 2018).

Other names

AML-reactive T cellsAnti-leukemic T cellsLeukemia-reactive cytotoxic T lymphocytesAML-infiltrating T cells

Activation and redirection of cytotoxic T-lymphocytes to recognize and eliminate AML blasts via MHC-dependent or MHC-independent pathways.