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Cancer Research Frontiers. 2016 May; 2(2): 226-251. doi: 10.17980/2016.226

Renewing the immunological approach to AML treatment: from novel pathways to innovative therapies

Alessandro Isidori1*, Federica Loscocco1, Marilena Ciciarello2, Giuseppe Visani1, Giulia Corradi2, Dorian Forte2, Mariangela Lecciso2, Darina Ocadlikova2, Sarah Parisi2, Valentina Salvestrini2, Margherita Parolini1, Michele Cavo2 and Antonio Curti2*.

1Haematology and Haematopoietic Stem Cell Transplant Center, AORMN, Pesaro, Italy;
2Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology “L. and A. Seràgnoli”, University of Bologna, Bologna, Italy.

 

*Corresponding authors: Alessandro Isidori, MD, PhD, Haematology and Haematopoietic Stem Cell Transplant Center, AORMN Marche Nord Hospital, Via Lombroso, 61100 Pesaro, Italy. Phone: +39-0721-364022; e-mail: asidori@gmail.com or Antonio Curti, MD, PhD, Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology “L. and A. Seràgnoli”, University of Bologna, Via Massarenti, 9, 40138, Bologna, Italy. Phone +39-051-6363680; e-mail: antonio.curti2@unibo.it

Citation: Alessandro Isidori, et al. Renewing the immunological approach to AML treatment: from novel pathways to innovative therapies. Cancer Research Frontiers. 2016 May; 2(2): 226-251. doi: 10.17980/2016.226

Copyright: @ 2016 Alessandro Isidori, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Competing Interests: the authors declare no competing interests.

Received Dec 29, 2015; Revised Mar 15, 2016; Accepted Mar 30, 2016. Published May 16, 2016

 

 

Abstract

Although in the last years major strides have been made in the understanding of the molecular basis of acute myeloid leukemia (AML), these relevant biological advances have had weak, if any, impact on the development of effective therapies for AML patients. Indeed, if the identification of molecular mutations within AML cell population has resulted in better risk-stratification, the vast majority of patients are treated with the same chemotherapy regimens and allogeneic stem cell transplant still represents the only curative option for intermediate and high-risk AML. In this context, increasing interest has gained the role that different cell components of the immune system may have for AML development and growth. In particular, a better knowledge of the mechanisms underlying the ability of AML cells of inducing immunological escape and systemic tolerance has been achieved. Based on these findings, the immunological way to the treatment of AML patients is becoming attractive and promising. The current review offers an overview of the tolerogenic mechanisms and pathways by focusing on those with potential clinical impact for the management of AML patients. Particularly, by moving from the biological significance of the underlying immunological pathways, we will discuss the clinical potential and application of a variety of different strategies, such as immunological checkpoint regulators, inhibitors of small molecules catabolism, i.e. indoleamine 2,3-dyoxigenase, anti-leukemia vaccines, adoptive immunotherapy with chimeric antigen receptor T cells and natural killer cells, monoclonal antibodies, including BiTEs engagers.

Keywords: acute myeloid leukemia, tumor immunity, immunotherapy, tolerance, monoclonal antibodies, vaccines, new drugs, cell therapy.

 

 

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