Immunotherapy in Acute Myeloid Leukemia: Where We Stand

Frontiers in Oncology

Guillermo Garcia-Manero¹  Elias Jabbour¹  Tapan Kadia¹  Naval Daver¹  Courtney DiNardo¹  Farhad Ravandi¹  Marina Konopleva¹  Alessandra Romano²  Giuseppe Visani³  Federica Loscocco³  Alessandro Isidori³  Hagop Kantarjian⁴  Claudio Cerchione⁴  Giovanni Martinelli⁴  Antonio Curti⁵  Adolfo de la Fuente Burguera⁶ 

[1] Department of Leukemia, MD Anderson Cancer Center, Houston, TX, United States;Dipartimento di Chirurgia e Specialità Medico-Chirurgiche, Sezione di Ematologia, Università degli Studi di Catania, Catania, Italy;Haematology and Stem Cell Transplant Center, AORMN, Pesaro, Italy;Hematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy;IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”, Bologna, Italy;MD Anderson Cancer Center, Madrid, Spain;

关键词: acute myeloid leukemia;    tolerance;    natural killer;    immunotherapy;    monoclonal antibody;    checkpoint inhibitors;   

DOI  :  10.3389/fonc.2021.656218

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown