Immunotherapy in Acute Myeloid Leukemia: Where We Stand
In the past few years, our improved knowledge of acute myeloid leukemia (AML) pathogenesis has led to the accelerated discovery of new drugs and the development of innovative therapeutic approaches. The role of the immune system in AML development, growth and recurrence has gained increasing interes...
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2021-05-01
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doaj-a6e56f3f011e4e9596bb57c9ced75c4c2021-05-10T08:00:57ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-05-011110.3389/fonc.2021.656218656218Immunotherapy in Acute Myeloid Leukemia: Where We StandAlessandro Isidori0Claudio Cerchione1Naval Daver2Courtney DiNardo3Guillermo Garcia-Manero4Marina Konopleva5Elias Jabbour6Farhad Ravandi7Tapan Kadia8Adolfo de la Fuente Burguera9Alessandra Romano10Federica Loscocco11Giuseppe Visani12Giovanni Martinelli13Hagop Kantarjian14Antonio Curti15Haematology and Stem Cell Transplant Center, AORMN, Pesaro, ItalyHematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, ItalyDepartment of Leukemia, MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Leukemia, MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Leukemia, MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Leukemia, MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Leukemia, MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Leukemia, MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Leukemia, MD Anderson Cancer Center, Houston, TX, United StatesMD Anderson Cancer Center, Madrid, SpainDipartimento di Chirurgia e Specialità Medico-Chirurgiche, Sezione di Ematologia, Università degli Studi di Catania, Catania, ItalyHaematology and Stem Cell Transplant Center, AORMN, Pesaro, ItalyHaematology and Stem Cell Transplant Center, AORMN, Pesaro, ItalyHematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, ItalyHematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”, Bologna, ItalyIn the past few years, our improved knowledge of acute myeloid leukemia (AML) pathogenesis has led to the accelerated discovery of new drugs and the development of innovative therapeutic approaches. The role of the immune system in AML development, growth and recurrence has gained increasing interest. A better understanding of immunological escape and systemic tolerance induced by AML blasts has been achieved. The extraordinary successes of immune therapies that harness the power of T cells in solid tumors and certain hematological malignancies have provided new stimuli in this area of research. Accordingly, major efforts have been made to develop immune therapies for the treatment of AML patients. The persistence of leukemia stem cells, representing the most relevant cause of relapse, even after allogeneic stem cell transplant (allo-SCT), remains a major hurdle in the path to cure for AML patients. Several clinical trials with immune-based therapies are currently ongoing in the frontline, relapsed/refractory, post-allo-SCT and minimal residual disease/maintenance setting, with the aim to improve survival of AML patients. This review summarizes the available data with immune-based therapeutic modalities such as monoclonal antibodies (naked and conjugated), T cell engagers, adoptive T-cell therapy, adoptive-NK therapy, checkpoint blockade via PD-1/PD-L1, CTLA4, TIM3 and macrophage checkpoint blockade via the CD47/SIRPa axis, and leukemia vaccines. Combining clinical results with biological immunological findings, possibly coupled with the discovery of biomarkers predictive for response, will hopefully allow us to determine the best approaches to immunotherapy in AML.https://www.frontiersin.org/articles/10.3389/fonc.2021.656218/fullacute myeloid leukemiatolerancenatural killerimmunotherapymonoclonal antibodycheckpoint inhibitors |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alessandro Isidori Claudio Cerchione Naval Daver Courtney DiNardo Guillermo Garcia-Manero Marina Konopleva Elias Jabbour Farhad Ravandi Tapan Kadia Adolfo de la Fuente Burguera Alessandra Romano Federica Loscocco Giuseppe Visani Giovanni Martinelli Hagop Kantarjian Antonio Curti |
spellingShingle |
Alessandro Isidori Claudio Cerchione Naval Daver Courtney DiNardo Guillermo Garcia-Manero Marina Konopleva Elias Jabbour Farhad Ravandi Tapan Kadia Adolfo de la Fuente Burguera Alessandra Romano Federica Loscocco Giuseppe Visani Giovanni Martinelli Hagop Kantarjian Antonio Curti Immunotherapy in Acute Myeloid Leukemia: Where We Stand Frontiers in Oncology acute myeloid leukemia tolerance natural killer immunotherapy monoclonal antibody checkpoint inhibitors |
author_facet |
Alessandro Isidori Claudio Cerchione Naval Daver Courtney DiNardo Guillermo Garcia-Manero Marina Konopleva Elias Jabbour Farhad Ravandi Tapan Kadia Adolfo de la Fuente Burguera Alessandra Romano Federica Loscocco Giuseppe Visani Giovanni Martinelli Hagop Kantarjian Antonio Curti |
author_sort |
Alessandro Isidori |
title |
Immunotherapy in Acute Myeloid Leukemia: Where We Stand |
title_short |
Immunotherapy in Acute Myeloid Leukemia: Where We Stand |
title_full |
Immunotherapy in Acute Myeloid Leukemia: Where We Stand |
title_fullStr |
Immunotherapy in Acute Myeloid Leukemia: Where We Stand |
title_full_unstemmed |
Immunotherapy in Acute Myeloid Leukemia: Where We Stand |
title_sort |
immunotherapy in acute myeloid leukemia: where we stand |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2021-05-01 |
description |
In the past few years, our improved knowledge of acute myeloid leukemia (AML) pathogenesis has led to the accelerated discovery of new drugs and the development of innovative therapeutic approaches. The role of the immune system in AML development, growth and recurrence has gained increasing interest. A better understanding of immunological escape and systemic tolerance induced by AML blasts has been achieved. The extraordinary successes of immune therapies that harness the power of T cells in solid tumors and certain hematological malignancies have provided new stimuli in this area of research. Accordingly, major efforts have been made to develop immune therapies for the treatment of AML patients. The persistence of leukemia stem cells, representing the most relevant cause of relapse, even after allogeneic stem cell transplant (allo-SCT), remains a major hurdle in the path to cure for AML patients. Several clinical trials with immune-based therapies are currently ongoing in the frontline, relapsed/refractory, post-allo-SCT and minimal residual disease/maintenance setting, with the aim to improve survival of AML patients. This review summarizes the available data with immune-based therapeutic modalities such as monoclonal antibodies (naked and conjugated), T cell engagers, adoptive T-cell therapy, adoptive-NK therapy, checkpoint blockade via PD-1/PD-L1, CTLA4, TIM3 and macrophage checkpoint blockade via the CD47/SIRPa axis, and leukemia vaccines. Combining clinical results with biological immunological findings, possibly coupled with the discovery of biomarkers predictive for response, will hopefully allow us to determine the best approaches to immunotherapy in AML. |
topic |
acute myeloid leukemia tolerance natural killer immunotherapy monoclonal antibody checkpoint inhibitors |
url |
https://www.frontiersin.org/articles/10.3389/fonc.2021.656218/full |
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