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

• Published in: Frontiers in immunology Vol. 12; p. 695051
• Main Authors: Limongello, Roberto, Marra, Andrea, Mancusi, Antonella, Bonato, Samanta, Hoxha, Eni, Ruggeri, Loredana, Hui, Susanta, Velardi, Andrea, Pierini, Antonio
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 03.08.2021
• Subjects: adoptive immune therapies; Biomarkers, Tumor - genetics; CAR-T; Cytokine-Induced Killer Cells - immunology; Cytokine-Induced Killer Cells - transplantation; Diffusion of Innovation; Genetic Predisposition to Disease; HR-AML; HSCT; Humans; Immunology; Immunotherapy, Adoptive - adverse effects; Immunotherapy, Adoptive - mortality; Killer Cells, Natural - immunology; Killer Cells, Natural - transplantation; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - immunology; Leukemia, Myeloid, Acute - mortality; Leukemia, Myeloid, Acute - therapy; Mutation; Phenotype; poor outcome; Receptors, Chimeric Antigen - genetics; Risk Assessment; Risk Factors; T-Lymphocytes - immunology; T-Lymphocytes - transplantation; Time Factors; Treatment Outcome; Treg-Tcon; poor outcome; HR-AML; adoptive immune therapies; CAR-T; HSCT; Treg-Tcon
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.695051

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 , 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.