TY - JOUR
T1 - Immunotherapy in Acute Myeloid Leukemia
T2 - Where We Stand
AU - Isidori, Alessandro
AU - Cerchione, Claudio
AU - Daver, Naval
AU - DiNardo, Courtney
AU - Garcia-Manero, Guillermo
AU - Konopleva, Marina
AU - Jabbour, Elias
AU - Ravandi, Farhad
AU - Kadia, Tapan
AU - Burguera, Adolfo de la Fuente
AU - Romano, Alessandra
AU - Loscocco, Federica
AU - Visani, Giuseppe
AU - Martinelli, Giovanni
AU - Kantarjian, Hagop
AU - Curti, Antonio
N1 - Publisher Copyright:
© Copyright © 2021 Isidori, Cerchione, Daver, DiNardo, Garcia-Manero, Konopleva, Jabbour, Ravandi, Kadia, Burguera, Romano, Loscocco, Visani, Martinelli, Kantarjian and Curti.
PY - 2021/5/10
Y1 - 2021/5/10
N2 - 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.
AB - 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.
KW - acute myeloid leukemia
KW - checkpoint inhibitors
KW - immunotherapy
KW - monoclonal antibody
KW - natural killer
KW - tolerance
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U2 - 10.3389/fonc.2021.656218
DO - 10.3389/fonc.2021.656218
M3 - Review article
C2 - 34041025
AN - SCOPUS:85107236160
SN - 2234-943X
VL - 11
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 656218
ER -