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Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab

CD38 is a transmembrane glycoprotein with ectoenzymatic activity involved in regulation of migration, signal transduction, and receptor-mediated adhesion. CD38 is highly expressed on various malignant cells, including multiple myeloma (MM), and at relatively low levels in other tissues, making it a...

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Autores principales: Martin, Thomas G., Corzo, Kathryn, Chiron, Marielle, van de Velde, Helgi, Abbadessa, Giovanni, Campana, Frank, Solanki, Malini, Meng, Robin, Lee, Helen, Wiederschain, Dmitri, Zhu, Chen, Rak, Alexey, Anderson, Kenneth C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953105/
https://www.ncbi.nlm.nih.gov/pubmed/31779273
http://dx.doi.org/10.3390/cells8121522
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author Martin, Thomas G.
Corzo, Kathryn
Chiron, Marielle
van de Velde, Helgi
Abbadessa, Giovanni
Campana, Frank
Solanki, Malini
Meng, Robin
Lee, Helen
Wiederschain, Dmitri
Zhu, Chen
Rak, Alexey
Anderson, Kenneth C.
author_facet Martin, Thomas G.
Corzo, Kathryn
Chiron, Marielle
van de Velde, Helgi
Abbadessa, Giovanni
Campana, Frank
Solanki, Malini
Meng, Robin
Lee, Helen
Wiederschain, Dmitri
Zhu, Chen
Rak, Alexey
Anderson, Kenneth C.
author_sort Martin, Thomas G.
collection PubMed
description CD38 is a transmembrane glycoprotein with ectoenzymatic activity involved in regulation of migration, signal transduction, and receptor-mediated adhesion. CD38 is highly expressed on various malignant cells, including multiple myeloma (MM), and at relatively low levels in other tissues, making it a suitable target for therapeutic antibodies. Several anti-CD38 therapies have been, or are being, developed for the treatment of MM, including daratumumab and isatuximab (SAR650984), respectively. Studies have shown that anti-CD38 therapies are effective in the treatment of relapsed/refractory MM and are well tolerated, with infusion reactions being the most common side effects. They can be used as monotherapy or in combination with immunomodulatory agents, such as pomalidomide, or proteasome inhibitors to potentiate their activity. Here we examine isatuximab and several anti-CD38 agents in development that were generated using new antibody engineering techniques and that may lead to more effective CD38 targeting. We also summarize trials assessing these antibodies in MM, other malignancies, and solid organ transplantation. Finally, we propose that further research on the mechanisms of resistance to anti-CD38 therapy and the development of biomarkers and new backbone regimens with CD38 antibodies will be important steps in building more personalized treatment for patients with MM.
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spelling pubmed-69531052020-01-23 Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab Martin, Thomas G. Corzo, Kathryn Chiron, Marielle van de Velde, Helgi Abbadessa, Giovanni Campana, Frank Solanki, Malini Meng, Robin Lee, Helen Wiederschain, Dmitri Zhu, Chen Rak, Alexey Anderson, Kenneth C. Cells Review CD38 is a transmembrane glycoprotein with ectoenzymatic activity involved in regulation of migration, signal transduction, and receptor-mediated adhesion. CD38 is highly expressed on various malignant cells, including multiple myeloma (MM), and at relatively low levels in other tissues, making it a suitable target for therapeutic antibodies. Several anti-CD38 therapies have been, or are being, developed for the treatment of MM, including daratumumab and isatuximab (SAR650984), respectively. Studies have shown that anti-CD38 therapies are effective in the treatment of relapsed/refractory MM and are well tolerated, with infusion reactions being the most common side effects. They can be used as monotherapy or in combination with immunomodulatory agents, such as pomalidomide, or proteasome inhibitors to potentiate their activity. Here we examine isatuximab and several anti-CD38 agents in development that were generated using new antibody engineering techniques and that may lead to more effective CD38 targeting. We also summarize trials assessing these antibodies in MM, other malignancies, and solid organ transplantation. Finally, we propose that further research on the mechanisms of resistance to anti-CD38 therapy and the development of biomarkers and new backbone regimens with CD38 antibodies will be important steps in building more personalized treatment for patients with MM. MDPI 2019-11-26 /pmc/articles/PMC6953105/ /pubmed/31779273 http://dx.doi.org/10.3390/cells8121522 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Martin, Thomas G.
Corzo, Kathryn
Chiron, Marielle
van de Velde, Helgi
Abbadessa, Giovanni
Campana, Frank
Solanki, Malini
Meng, Robin
Lee, Helen
Wiederschain, Dmitri
Zhu, Chen
Rak, Alexey
Anderson, Kenneth C.
Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab
title Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab
title_full Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab
title_fullStr Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab
title_full_unstemmed Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab
title_short Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab
title_sort therapeutic opportunities with pharmacological inhibition of cd38 with isatuximab
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953105/
https://www.ncbi.nlm.nih.gov/pubmed/31779273
http://dx.doi.org/10.3390/cells8121522
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