Profile of elotuzumab and its potential in the treatment of multiple myeloma

Yi-Chang Liu,1,2 Susann Szmania,1 Frits van Rhee1 1Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 2Faculty of Medicine, College of Medicine, Kaohsiung Medical University and Department of Hematology-Oncology, Kaohsiung Medical Universi...

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Autores principales:	Liu YC, Szmania S, van Rhee F
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Diseases of the blood and blood-forming organs RC633-647.5
Acceso en línea:	https://doaj.org/article/f0a582c441c74bf3ba409f69f79afbc1
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spelling	oai:doaj.org-article:f0a582c441c74bf3ba409f69f79afbc12021-12-02T05:11:18ZProfile of elotuzumab and its potential in the treatment of multiple myeloma1179-9889https://doaj.org/article/f0a582c441c74bf3ba409f69f79afbc12014-06-01T00:00:00Zhttp://www.dovepress.com/profile-of-elotuzumab-and-its-potential-in-the-treatment-of-multiple-m-a17084https://doaj.org/toc/1179-9889 Yi-Chang Liu,1,2 Susann Szmania,1 Frits van Rhee1 1Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 2Faculty of Medicine, College of Medicine, Kaohsiung Medical University and Department of Hematology-Oncology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Abstract: Although the introduction of novel drugs has improved outcome significantly in multiple myeloma (MM), many patients still eventually relapse. Monoclonal antibodies (mAbs) targeting MM-related antigens can complement currently available therapies. CS1 (also known as CD2 subunit 1, SLAMF7, CD319, and CRACC), a cell surface glycoprotein receptor that is a member of the signaling lymphocytic activation molecule (SLAM) family, is highly and nearly uniformly expressed in myeloma cells at the gene and protein level, but not expressed in other tissues, including hematopoietic stem cells, making CS1 a compelling target for the design of immunotherapies directed at MM. Elotuzumab (formerly HuLuc63), which is a humanized IgG1 mAb recognizing the extracellular region of human CS1, has been shown to be effective in preclinical and early stage clinical investigations, and its efficacy and safety will be further validated in ongoing Phase III trials. Integration of elotuzumab into multidrug therapeutic paradigms seems logical, as elotuzumab is more effective when combined with other agents, such as immunomodulatory drugs or proteasome inhibitors. The functional role of CS1 in MM pathogenesis and the consequences of elotuzumab on normal immune cells should be further investigated. Identification of potential biomarkers and exploration of resistance mechanisms are important issues for elotuzumab-based therapies, as is determining the best clinical placement of elotuzumab, not only in the relapsed/refractory setting but also in upfront therapy for high-risk frank MM, smoldering MM at high-risk of progression, and in maintenance regimens. This review will cover the biological characteristics of CS1 in normal immune cells and MM cells, the efficacy profile and mechanisms of action of elotuzumab from preclinical and clinical investigations, and its potential impact on the treatment of MM. Keywords: CS1, monoclonal antibody, immunotherapyLiu YCSzmania Svan Rhee FDove Medical PressarticleDiseases of the blood and blood-forming organsRC633-647.5ENBlood and Lymphatic Cancer: Targets and Therapy, Vol 2014, Iss default, Pp 15-27 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diseases of the blood and blood-forming organs RC633-647.5
spellingShingle	Diseases of the blood and blood-forming organs RC633-647.5 Liu YC Szmania S van Rhee F Profile of elotuzumab and its potential in the treatment of multiple myeloma
description	Yi-Chang Liu,1,2 Susann Szmania,1 Frits van Rhee1 1Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 2Faculty of Medicine, College of Medicine, Kaohsiung Medical University and Department of Hematology-Oncology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Abstract: Although the introduction of novel drugs has improved outcome significantly in multiple myeloma (MM), many patients still eventually relapse. Monoclonal antibodies (mAbs) targeting MM-related antigens can complement currently available therapies. CS1 (also known as CD2 subunit 1, SLAMF7, CD319, and CRACC), a cell surface glycoprotein receptor that is a member of the signaling lymphocytic activation molecule (SLAM) family, is highly and nearly uniformly expressed in myeloma cells at the gene and protein level, but not expressed in other tissues, including hematopoietic stem cells, making CS1 a compelling target for the design of immunotherapies directed at MM. Elotuzumab (formerly HuLuc63), which is a humanized IgG1 mAb recognizing the extracellular region of human CS1, has been shown to be effective in preclinical and early stage clinical investigations, and its efficacy and safety will be further validated in ongoing Phase III trials. Integration of elotuzumab into multidrug therapeutic paradigms seems logical, as elotuzumab is more effective when combined with other agents, such as immunomodulatory drugs or proteasome inhibitors. The functional role of CS1 in MM pathogenesis and the consequences of elotuzumab on normal immune cells should be further investigated. Identification of potential biomarkers and exploration of resistance mechanisms are important issues for elotuzumab-based therapies, as is determining the best clinical placement of elotuzumab, not only in the relapsed/refractory setting but also in upfront therapy for high-risk frank MM, smoldering MM at high-risk of progression, and in maintenance regimens. This review will cover the biological characteristics of CS1 in normal immune cells and MM cells, the efficacy profile and mechanisms of action of elotuzumab from preclinical and clinical investigations, and its potential impact on the treatment of MM. Keywords: CS1, monoclonal antibody, immunotherapy
format	article
author	Liu YC Szmania S van Rhee F
author_facet	Liu YC Szmania S van Rhee F
author_sort	Liu YC
title	Profile of elotuzumab and its potential in the treatment of multiple myeloma
title_short	Profile of elotuzumab and its potential in the treatment of multiple myeloma
title_full	Profile of elotuzumab and its potential in the treatment of multiple myeloma
title_fullStr	Profile of elotuzumab and its potential in the treatment of multiple myeloma
title_full_unstemmed	Profile of elotuzumab and its potential in the treatment of multiple myeloma
title_sort	profile of elotuzumab and its potential in the treatment of multiple myeloma
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/f0a582c441c74bf3ba409f69f79afbc1
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Profile of elotuzumab and its potential in the treatment of multiple myeloma

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