title: Targeted immunotherapy for acute myeloid leukemia.
abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) demonstrated convincingly the potential of allogeneic T cells in causing sustained remissions in high-risk hematologic malignancies. However toxicity of allogeneic HSCT limits its application to a broader group of patients. An improved understanding of NK biology along with mechanisms of natural killer (NK) cell and T-cell-mediated alloreactivity against leukemia has led to several clinical immunotherapeutic strategies that preserve graft versus leukemia (GVL) while minimizing the toxicity of HSCT. Here we review strategies being explored both in HSCT and non-HSCT settings that include an emphasis on two key aspects: (a) Maximizing cytotoxicity of alloreactive cells, ie, NK cells and T cells, and (b) Targeted manipulation of critical pathways in T and NK cells contributing to sustained anti-leukemia effects.
authors: Department of Internal Medicine, The Ohio State University, Columbus, USA.
authors: Sumithira
authors: S
authors: Vasu
authors: Michael A
authors: MA
authors: Caligiuri
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology; D006086:Graft vs Host Disease / Q000517:prevention & control*; D020544:Graft vs Leukemia Effect / Q000187:drug effects / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D051379:Mice; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D054340:Receptors, KIR / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014481:United States
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D054340:Receptors, KIR