Monoclonal anti-CD38 therapy in human myeloma: retrospects and prospects
Monoclonal antibody therapy using CD38 as a target remains central to managing human multiple myeloma (MM). CD38 was selected early on as a target for mAb-mediated therapy for MM, driven by findings from an early Cluster of Differentiation (CD) Workshop. The first CD38-targeting antibody to be appro...
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| Format: | Article |
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1519300/full |
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| author | Alberto L. Horenstein Angelo C. Faini Angelo C. Faini Fabio Morandi Erika Ortolan Paola Storti Nicola Giuliani Nicola Giuliani Paul G. Richardson Fabio Malavasi Fabio Malavasi |
| author_facet | Alberto L. Horenstein Angelo C. Faini Angelo C. Faini Fabio Morandi Erika Ortolan Paola Storti Nicola Giuliani Nicola Giuliani Paul G. Richardson Fabio Malavasi Fabio Malavasi |
| author_sort | Alberto L. Horenstein |
| collection | DOAJ |
| description | Monoclonal antibody therapy using CD38 as a target remains central to managing human multiple myeloma (MM). CD38 was selected early on as a target for mAb-mediated therapy for MM, driven by findings from an early Cluster of Differentiation (CD) Workshop. The first CD38-targeting antibody to be approved yielded strong trial results, significantly improving survival rates and earning widespread patient acceptance. However, resistance to the therapy later emerged, complicating treatment management. Despite CD38’s still central role in MM therapy, too little attention has been paid to its broader roles–not only as a myeloma marker but also as an enzyme and adhesion molecule in physiology. This review, a collaborative effort between basic scientists and clinical experts, explores some of the lesser-known mechanisms of antibody action and interactions with CD38 at key stages of treatment. The review also highlights the relevance of the MM environment, focusing on the importance of the bone marrow (BM) niche. The goal is to identify new agents whose unique properties may enhance tumor eradication. By gaining a deeper understanding of interactions between therapeutic antibodies, myeloma cells, and the tumor microenvironment (TME), it is hoped that previously unrecognized vulnerabilities within the disease may be revealed, paving the way to more effective treatment strategies. |
| format | Article |
| id | doaj-art-59908895205e40ee95e98451fc42a7db |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-59908895205e40ee95e98451fc42a7db2025-02-12T07:25:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15193001519300Monoclonal anti-CD38 therapy in human myeloma: retrospects and prospectsAlberto L. Horenstein0Angelo C. Faini1Angelo C. Faini2Fabio Morandi3Erika Ortolan4Paola Storti5Nicola Giuliani6Nicola Giuliani7Paul G. Richardson8Fabio Malavasi9Fabio Malavasi10Lab of Immunogenetics, Department of Medical Sciences, University of Torino, Torino, ItalyLab of Immunogenetics, Department of Medical Sciences, University of Torino, Torino, ItalyImmunogenetics and Transplant Biology, University Hospital “Città della Salute e della Scienza di Torino”, Torino, ItalyUOSD Laboratorio di Terapie Cellulari, IRCCS Istituto Giannina Gaslini, Genova, ItalyLab of Immunogenetics, Department of Medical Sciences, University of Torino, Torino, ItalyDepartment of Medicine and Surgery, University of Parma, Parma, ItalyDepartment of Medicine and Surgery, University of Parma, Parma, ItalyDepartment of Medicine and Surgery, University of Parma & Multiple Myeloma Program, AOU, Parma, ItalyJerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, United StatesLab of Immunogenetics, Department of Medical Sciences, University of Torino, Torino, ItalyFondazione Ricerca Molinette Ets, Torino, ItalyMonoclonal antibody therapy using CD38 as a target remains central to managing human multiple myeloma (MM). CD38 was selected early on as a target for mAb-mediated therapy for MM, driven by findings from an early Cluster of Differentiation (CD) Workshop. The first CD38-targeting antibody to be approved yielded strong trial results, significantly improving survival rates and earning widespread patient acceptance. However, resistance to the therapy later emerged, complicating treatment management. Despite CD38’s still central role in MM therapy, too little attention has been paid to its broader roles–not only as a myeloma marker but also as an enzyme and adhesion molecule in physiology. This review, a collaborative effort between basic scientists and clinical experts, explores some of the lesser-known mechanisms of antibody action and interactions with CD38 at key stages of treatment. The review also highlights the relevance of the MM environment, focusing on the importance of the bone marrow (BM) niche. The goal is to identify new agents whose unique properties may enhance tumor eradication. By gaining a deeper understanding of interactions between therapeutic antibodies, myeloma cells, and the tumor microenvironment (TME), it is hoped that previously unrecognized vulnerabilities within the disease may be revealed, paving the way to more effective treatment strategies.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1519300/fullantibody therapiesCD38 monoclonal antibodiesIgG Fc receptorsectoenzymatic activitymultiple myeloma |
| spellingShingle | Alberto L. Horenstein Angelo C. Faini Angelo C. Faini Fabio Morandi Erika Ortolan Paola Storti Nicola Giuliani Nicola Giuliani Paul G. Richardson Fabio Malavasi Fabio Malavasi Monoclonal anti-CD38 therapy in human myeloma: retrospects and prospects Frontiers in Immunology antibody therapies CD38 monoclonal antibodies IgG Fc receptors ectoenzymatic activity multiple myeloma |
| title | Monoclonal anti-CD38 therapy in human myeloma: retrospects and prospects |
| title_full | Monoclonal anti-CD38 therapy in human myeloma: retrospects and prospects |
| title_fullStr | Monoclonal anti-CD38 therapy in human myeloma: retrospects and prospects |
| title_full_unstemmed | Monoclonal anti-CD38 therapy in human myeloma: retrospects and prospects |
| title_short | Monoclonal anti-CD38 therapy in human myeloma: retrospects and prospects |
| title_sort | monoclonal anti cd38 therapy in human myeloma retrospects and prospects |
| topic | antibody therapies CD38 monoclonal antibodies IgG Fc receptors ectoenzymatic activity multiple myeloma |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1519300/full |
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