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New Frontiers in Monoclonal Antibodies for the Targeted Therapy of Acute Myeloid Leukemia and Myelodysplastic Syndromes

Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represent an unmet clinical need whose prognosis is still dismal. Alterations of immune response play a prominent role in AML/MDS pathogenesis, revealing novel options for immunotherapy. Among immune system regulators, CD47, immune che...

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Autores principales: Gallazzi, Marco, Ucciero, Maghalie Anais Marie, Faraci, Danilo Giuseppe, Mahmoud, Abdurraouf Mokhtar, Al Essa, Wael, Gaidano, Gianluca, Mouhssine, Samir, Crisà, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320300/
https://www.ncbi.nlm.nih.gov/pubmed/35886899
http://dx.doi.org/10.3390/ijms23147542
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author Gallazzi, Marco
Ucciero, Maghalie Anais Marie
Faraci, Danilo Giuseppe
Mahmoud, Abdurraouf Mokhtar
Al Essa, Wael
Gaidano, Gianluca
Mouhssine, Samir
Crisà, Elena
author_facet Gallazzi, Marco
Ucciero, Maghalie Anais Marie
Faraci, Danilo Giuseppe
Mahmoud, Abdurraouf Mokhtar
Al Essa, Wael
Gaidano, Gianluca
Mouhssine, Samir
Crisà, Elena
author_sort Gallazzi, Marco
collection PubMed
description Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represent an unmet clinical need whose prognosis is still dismal. Alterations of immune response play a prominent role in AML/MDS pathogenesis, revealing novel options for immunotherapy. Among immune system regulators, CD47, immune checkpoints, and toll-like receptor 2 (TLR2) are major targets. Magrolimab antagonizes CD47, which is overexpressed by AML and MDS cells, thus inducing macrophage phagocytosis with clinical activity in AML/MDS. Sabatolimab, an inhibitor of T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), which disrupts its binding to galectin-9, has shown promising results in AML/MDS, enhancing the effector functions of lymphocytes and triggering tumor cell death. Several other surface molecules, namely CD33, CD123, CD45, and CD70, can be targeted with monoclonal antibodies (mAbs) that exert different mechanisms of action and include naked and conjugated antibodies, bispecific T-cell engagers, trispecific killer engagers, and fusion proteins linked to toxins. These novel mAbs are currently under investigation for use as monotherapy or in combination with hypomethylating agents, BCL2 inhibitors, and chemotherapy in various clinical trials at different phases of development. Here, we review the main molecular targets and modes of action of novel mAb-based immunotherapies, which can represent the future of AML and higher risk MDS treatment.
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spelling pubmed-93203002022-07-27 New Frontiers in Monoclonal Antibodies for the Targeted Therapy of Acute Myeloid Leukemia and Myelodysplastic Syndromes Gallazzi, Marco Ucciero, Maghalie Anais Marie Faraci, Danilo Giuseppe Mahmoud, Abdurraouf Mokhtar Al Essa, Wael Gaidano, Gianluca Mouhssine, Samir Crisà, Elena Int J Mol Sci Review Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represent an unmet clinical need whose prognosis is still dismal. Alterations of immune response play a prominent role in AML/MDS pathogenesis, revealing novel options for immunotherapy. Among immune system regulators, CD47, immune checkpoints, and toll-like receptor 2 (TLR2) are major targets. Magrolimab antagonizes CD47, which is overexpressed by AML and MDS cells, thus inducing macrophage phagocytosis with clinical activity in AML/MDS. Sabatolimab, an inhibitor of T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), which disrupts its binding to galectin-9, has shown promising results in AML/MDS, enhancing the effector functions of lymphocytes and triggering tumor cell death. Several other surface molecules, namely CD33, CD123, CD45, and CD70, can be targeted with monoclonal antibodies (mAbs) that exert different mechanisms of action and include naked and conjugated antibodies, bispecific T-cell engagers, trispecific killer engagers, and fusion proteins linked to toxins. These novel mAbs are currently under investigation for use as monotherapy or in combination with hypomethylating agents, BCL2 inhibitors, and chemotherapy in various clinical trials at different phases of development. Here, we review the main molecular targets and modes of action of novel mAb-based immunotherapies, which can represent the future of AML and higher risk MDS treatment. MDPI 2022-07-07 /pmc/articles/PMC9320300/ /pubmed/35886899 http://dx.doi.org/10.3390/ijms23147542 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Gallazzi, Marco
Ucciero, Maghalie Anais Marie
Faraci, Danilo Giuseppe
Mahmoud, Abdurraouf Mokhtar
Al Essa, Wael
Gaidano, Gianluca
Mouhssine, Samir
Crisà, Elena
New Frontiers in Monoclonal Antibodies for the Targeted Therapy of Acute Myeloid Leukemia and Myelodysplastic Syndromes
title New Frontiers in Monoclonal Antibodies for the Targeted Therapy of Acute Myeloid Leukemia and Myelodysplastic Syndromes
title_full New Frontiers in Monoclonal Antibodies for the Targeted Therapy of Acute Myeloid Leukemia and Myelodysplastic Syndromes
title_fullStr New Frontiers in Monoclonal Antibodies for the Targeted Therapy of Acute Myeloid Leukemia and Myelodysplastic Syndromes
title_full_unstemmed New Frontiers in Monoclonal Antibodies for the Targeted Therapy of Acute Myeloid Leukemia and Myelodysplastic Syndromes
title_short New Frontiers in Monoclonal Antibodies for the Targeted Therapy of Acute Myeloid Leukemia and Myelodysplastic Syndromes
title_sort new frontiers in monoclonal antibodies for the targeted therapy of acute myeloid leukemia and myelodysplastic syndromes
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320300/
https://www.ncbi.nlm.nih.gov/pubmed/35886899
http://dx.doi.org/10.3390/ijms23147542
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