Adverse genetic risk acute myeloid leukemia (AML) includes a wide range of clinical-pathological entities with extremely poor outcomes; thus, novel therapeutic approaches are needed. Promising results achieved by engineered chimeric antigen receptor (CAR) T cells in other blood neoplasms have paved the way for the development of immune cell-based therapies for adverse genetic risk AML. Among these, adoptive cell immunotherapies with single/multiple CAR-T cells, CAR-natural killer (NK) cells, cytokine-induced killer cells (CIK), and NK cells are subjects of ongoing clinical trials. On the other hand, allogeneic hematopoietic stem cell transplantation (allo-HSCT) still represents the only curative option for adverse genetic risk AML patients. Unfortunately, high relapse rates (above 50%) and associated dismal outcomes (reported survival ~10–20%) even question the role of current allo-HSCT protocols and emphasize the urgency of adopting novel effective transplant strategies. We have recently demonstrated that haploidentical allo-HSCT combined with regulatory and conventional T cells adoptive immunotherapy (Treg-Tcon haplo-HSCT) is able to overcome disease-intrinsic chemoresistance, prevent leukemia-relapse, and improve survival of adverse genetic risk AML patients. In this Perspective, we briefly review the recent advancements with immune cell-based strategies against adverse genetic risk AML and discuss how such approaches could favorably impact on patients’ outcomes.

Novel Immune Cell-Based Therapies to Eradicate High-Risk Acute Myeloid Leukemia

Limongello R.;Marra A.;Mancusi A.;Bonato S.;Hoxha E.;Ruggeri L.;Velardi A.;Pierini A.
2021

Abstract

Adverse genetic risk acute myeloid leukemia (AML) includes a wide range of clinical-pathological entities with extremely poor outcomes; thus, novel therapeutic approaches are needed. Promising results achieved by engineered chimeric antigen receptor (CAR) T cells in other blood neoplasms have paved the way for the development of immune cell-based therapies for adverse genetic risk AML. Among these, adoptive cell immunotherapies with single/multiple CAR-T cells, CAR-natural killer (NK) cells, cytokine-induced killer cells (CIK), and NK cells are subjects of ongoing clinical trials. On the other hand, allogeneic hematopoietic stem cell transplantation (allo-HSCT) still represents the only curative option for adverse genetic risk AML patients. Unfortunately, high relapse rates (above 50%) and associated dismal outcomes (reported survival ~10–20%) even question the role of current allo-HSCT protocols and emphasize the urgency of adopting novel effective transplant strategies. We have recently demonstrated that haploidentical allo-HSCT combined with regulatory and conventional T cells adoptive immunotherapy (Treg-Tcon haplo-HSCT) is able to overcome disease-intrinsic chemoresistance, prevent leukemia-relapse, and improve survival of adverse genetic risk AML patients. In this Perspective, we briefly review the recent advancements with immune cell-based strategies against adverse genetic risk AML and discuss how such approaches could favorably impact on patients’ outcomes.
2021
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11391/1549593
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