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Monoclonal antibodies targeting CD38 in hematological malignancies and beyond

CD38 is a multifunctional cell surface protein that has receptor as well as enzyme functions. The protein is generally expressed at low levels on various hematological and solid tissues, while plasma cells express particularly high levels of CD38. The protein is also expressed in a subset of hematol...

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Autores principales: van de Donk, Niels W. C. J., Janmaat, Maarten L., Mutis, Tuna, Lammerts van Bueren, Jeroen J., Ahmadi, Tahamtan, Sasser, A. Kate, Lokhorst, Henk M., Parren, Paul W. H. I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755228/
https://www.ncbi.nlm.nih.gov/pubmed/26864107
http://dx.doi.org/10.1111/imr.12389
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author van de Donk, Niels W. C. J.
Janmaat, Maarten L.
Mutis, Tuna
Lammerts van Bueren, Jeroen J.
Ahmadi, Tahamtan
Sasser, A. Kate
Lokhorst, Henk M.
Parren, Paul W. H. I.
author_facet van de Donk, Niels W. C. J.
Janmaat, Maarten L.
Mutis, Tuna
Lammerts van Bueren, Jeroen J.
Ahmadi, Tahamtan
Sasser, A. Kate
Lokhorst, Henk M.
Parren, Paul W. H. I.
author_sort van de Donk, Niels W. C. J.
collection PubMed
description CD38 is a multifunctional cell surface protein that has receptor as well as enzyme functions. The protein is generally expressed at low levels on various hematological and solid tissues, while plasma cells express particularly high levels of CD38. The protein is also expressed in a subset of hematological tumors, and shows especially broad and high expression levels in plasma cell tumors such as multiple myeloma (MM). Together, this triggered the development of various therapeutic CD38 antibodies, including daratumumab, isatuximab, and MOR202. Daratumumab binds a unique CD38 epitope and showed strong anti‐tumor activity in preclinical models. The antibody engages diverse mechanisms of action, including complement‐dependent cytotoxicity, antibody‐dependent cellular cytotoxicity, antibody‐dependent cellular phagocytosis, programmed cell death, modulation of enzymatic activity, and immunomodulatory activity. CD38‐targeting antibodies have a favorable toxicity profile in patients, and early clinical data show a marked activity in MM, while studies in other hematological malignancies are ongoing. Daratumumab has single agent activity and a limited toxicity profile, allowing favorable combination therapies with existing as well as emerging therapies, which are currently evaluated in the clinic. Finally, CD38 antibodies may have a role in the treatment of diseases beyond hematological malignancies, including solid tumors and antibody‐mediated autoimmune diseases.
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spelling pubmed-47552282016-02-25 Monoclonal antibodies targeting CD38 in hematological malignancies and beyond van de Donk, Niels W. C. J. Janmaat, Maarten L. Mutis, Tuna Lammerts van Bueren, Jeroen J. Ahmadi, Tahamtan Sasser, A. Kate Lokhorst, Henk M. Parren, Paul W. H. I. Immunol Rev Invited Reviews CD38 is a multifunctional cell surface protein that has receptor as well as enzyme functions. The protein is generally expressed at low levels on various hematological and solid tissues, while plasma cells express particularly high levels of CD38. The protein is also expressed in a subset of hematological tumors, and shows especially broad and high expression levels in plasma cell tumors such as multiple myeloma (MM). Together, this triggered the development of various therapeutic CD38 antibodies, including daratumumab, isatuximab, and MOR202. Daratumumab binds a unique CD38 epitope and showed strong anti‐tumor activity in preclinical models. The antibody engages diverse mechanisms of action, including complement‐dependent cytotoxicity, antibody‐dependent cellular cytotoxicity, antibody‐dependent cellular phagocytosis, programmed cell death, modulation of enzymatic activity, and immunomodulatory activity. CD38‐targeting antibodies have a favorable toxicity profile in patients, and early clinical data show a marked activity in MM, while studies in other hematological malignancies are ongoing. Daratumumab has single agent activity and a limited toxicity profile, allowing favorable combination therapies with existing as well as emerging therapies, which are currently evaluated in the clinic. Finally, CD38 antibodies may have a role in the treatment of diseases beyond hematological malignancies, including solid tumors and antibody‐mediated autoimmune diseases. John Wiley and Sons Inc. 2016-02-10 2016-03 /pmc/articles/PMC4755228/ /pubmed/26864107 http://dx.doi.org/10.1111/imr.12389 Text en © 2016 Genmab, Utrecht, the Netherlands. Immunological Reviews published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Invited Reviews
van de Donk, Niels W. C. J.
Janmaat, Maarten L.
Mutis, Tuna
Lammerts van Bueren, Jeroen J.
Ahmadi, Tahamtan
Sasser, A. Kate
Lokhorst, Henk M.
Parren, Paul W. H. I.
Monoclonal antibodies targeting CD38 in hematological malignancies and beyond
title Monoclonal antibodies targeting CD38 in hematological malignancies and beyond
title_full Monoclonal antibodies targeting CD38 in hematological malignancies and beyond
title_fullStr Monoclonal antibodies targeting CD38 in hematological malignancies and beyond
title_full_unstemmed Monoclonal antibodies targeting CD38 in hematological malignancies and beyond
title_short Monoclonal antibodies targeting CD38 in hematological malignancies and beyond
title_sort monoclonal antibodies targeting cd38 in hematological malignancies and beyond
topic Invited Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755228/
https://www.ncbi.nlm.nih.gov/pubmed/26864107
http://dx.doi.org/10.1111/imr.12389
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