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Innovative Anti-CD38 and Anti-BCMA Targeted Therapies in Multiple Myeloma: Mechanisms of Action and Resistance
CD38 and B-cell maturation antigens (BCMAs) are prevalently expressed on neoplastic plasma cells in multiple myeloma (MM), making them ideal therapeutic targets. Anti-CD38 monoclonal antibodies, such as approved daratumumab and isatuximab, are currently the milestone in MM treatment because they ind...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820921/ https://www.ncbi.nlm.nih.gov/pubmed/36614086 http://dx.doi.org/10.3390/ijms24010645 |
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author | De Novellis, Danilo Fontana, Raffaele Giudice, Valentina Serio, Bianca Selleri, Carmine |
author_facet | De Novellis, Danilo Fontana, Raffaele Giudice, Valentina Serio, Bianca Selleri, Carmine |
author_sort | De Novellis, Danilo |
collection | PubMed |
description | CD38 and B-cell maturation antigens (BCMAs) are prevalently expressed on neoplastic plasma cells in multiple myeloma (MM), making them ideal therapeutic targets. Anti-CD38 monoclonal antibodies, such as approved daratumumab and isatuximab, are currently the milestone in MM treatment because they induce plasma cell apoptosis and kill through several mechanisms, including antibody-dependent cellular cytotoxicity or phagocytosis. BCMA is considered an excellent target in MM, and three different therapeutic strategies are either already available in clinical practice or under investigation: antibody–drug conjugates, such as belantamab-mafodotin; bispecific T cell engagers; and chimeric antigen receptor-modified T cell therapies. Despite the impressive clinical efficacy of these new strategies in the treatment of newly diagnosed or multi-refractory MM patients, several mechanisms of resistance have already been described, including antigen downregulation, the impairment of antibody-dependent cell cytotoxicity and phagocytosis, T- and natural killer cell senescence, and exhaustion. In this review, we summarize the current knowledge on the mechanisms of action and resistance of anti-CD38 and anti-BCMA agents and their clinical efficacy and safety. |
format | Online Article Text |
id | pubmed-9820921 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98209212023-01-07 Innovative Anti-CD38 and Anti-BCMA Targeted Therapies in Multiple Myeloma: Mechanisms of Action and Resistance De Novellis, Danilo Fontana, Raffaele Giudice, Valentina Serio, Bianca Selleri, Carmine Int J Mol Sci Review CD38 and B-cell maturation antigens (BCMAs) are prevalently expressed on neoplastic plasma cells in multiple myeloma (MM), making them ideal therapeutic targets. Anti-CD38 monoclonal antibodies, such as approved daratumumab and isatuximab, are currently the milestone in MM treatment because they induce plasma cell apoptosis and kill through several mechanisms, including antibody-dependent cellular cytotoxicity or phagocytosis. BCMA is considered an excellent target in MM, and three different therapeutic strategies are either already available in clinical practice or under investigation: antibody–drug conjugates, such as belantamab-mafodotin; bispecific T cell engagers; and chimeric antigen receptor-modified T cell therapies. Despite the impressive clinical efficacy of these new strategies in the treatment of newly diagnosed or multi-refractory MM patients, several mechanisms of resistance have already been described, including antigen downregulation, the impairment of antibody-dependent cell cytotoxicity and phagocytosis, T- and natural killer cell senescence, and exhaustion. In this review, we summarize the current knowledge on the mechanisms of action and resistance of anti-CD38 and anti-BCMA agents and their clinical efficacy and safety. MDPI 2022-12-30 /pmc/articles/PMC9820921/ /pubmed/36614086 http://dx.doi.org/10.3390/ijms24010645 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 De Novellis, Danilo Fontana, Raffaele Giudice, Valentina Serio, Bianca Selleri, Carmine Innovative Anti-CD38 and Anti-BCMA Targeted Therapies in Multiple Myeloma: Mechanisms of Action and Resistance |
title | Innovative Anti-CD38 and Anti-BCMA Targeted Therapies in Multiple Myeloma: Mechanisms of Action and Resistance |
title_full | Innovative Anti-CD38 and Anti-BCMA Targeted Therapies in Multiple Myeloma: Mechanisms of Action and Resistance |
title_fullStr | Innovative Anti-CD38 and Anti-BCMA Targeted Therapies in Multiple Myeloma: Mechanisms of Action and Resistance |
title_full_unstemmed | Innovative Anti-CD38 and Anti-BCMA Targeted Therapies in Multiple Myeloma: Mechanisms of Action and Resistance |
title_short | Innovative Anti-CD38 and Anti-BCMA Targeted Therapies in Multiple Myeloma: Mechanisms of Action and Resistance |
title_sort | innovative anti-cd38 and anti-bcma targeted therapies in multiple myeloma: mechanisms of action and resistance |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820921/ https://www.ncbi.nlm.nih.gov/pubmed/36614086 http://dx.doi.org/10.3390/ijms24010645 |
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