The Graft-Versus-Leukemia Effect in AML

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is the most established and commonly used cellular immunotherapy in cancer care. It is the most potent anti-leukemic therapy in patients with acute myeloid leukemia (AML) and is routinely used with curative intent in patients with intermediate and poor risk disease. Donor T cells, and possibly other immune cells, eliminate residual leukemia cells after prior (radio)chemotherapy. This immune-mediated response is known as graft-versus-leukemia (GvL). Donor alloimmune responses can also be directed against healthy tissues, which is known as graft-versus-host disease (GvHD). GvHD and GvL often co-occur and, therefore, a major barrier to exploiting the full immunotherapeutic benefit of donor immune cells against patient leukemia is the immunosuppression required to treat GvHD. However, curative responses to allo-SCT and GvHD do not always occur together, suggesting that these two immune responses could be de-coupled in some patients. To make further progress in successfully promoting GvL without GvHD, we must transform our limited understanding of the cellular and molecular basis of GvL and GvHD. Specifically, in most patients we do not understand the antigenic basis of immune responses in GvL and GvHD. Identification of antigens important for GvL but not GvHD, and vice versa, could impact on donor selection, allow us to track GvL immune responses and begin to specifically harness and strengthen anti-leukemic immune responses against patient AML cells, whilst minimizing the toxicity of GvHD.

A modular and controllable T cell therapy platform for acute myeloid leukemia

“…Donor T cell alloreactivity driving the graft-versusleukemia effect is a major mechanism behind the curative effect of allo-SCT, and supports the notion that T cells are crucial effector cells in the context of AML therapy [37,38]. Importantly, there is strong Unt T cells and αE3-αCD123…”

Genetic and Molecular Basis of Heterogeneous NK Cell Responses against Acute Leukemia

“…On the basis of clinical data, NK cells appear to play a crucial role in the eradication of acute leukemia [ 26 , 27 , 28 ]. However, the ability of NK cells to mediate a response against tumor cells such as leukemia cells depends on the presence of ligands that are recognized by NK receptors on tumor cells [ 12 , 13 , 26 , 29 ].…”

Independent human mesenchymal stromal cell-derived extracellular vesicle preparations differentially affect symptoms in an advanced murine Graft-versus-Host-Disease model

“…Allogeneic hematopoietic stem cell transplantation (alloSCT) is the most frequently applied cell-based therapy. For now, it is conducted to treat more than 70 malignant and nonmalignant hematologic diseases, including leukaemia and lymphoma (Sweeney and Vyas, 2019). In many cases, it is considered as the only therapy offering curative perspectives.…”