{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T05:45:10Z","timestamp":1791870310273,"version":"4.3.4"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: CD38-targeting monoclonal antibodies isatuximab and daratumumab have revolutionized multiple myeloma (MM) treatment, but a deeper understanding of their distinct mechanisms is crucial for therapeutic optimization. Methods: We used flow cytometry to assess isatuximab and daratumumab binding competition in MM cell lines and patient-derived bone marrow cells. The dynamics of CD38 expression were evaluated at different time points before and after antibody-mediated removal. The effects of IMiDs (pomalidomide, lenalidomide) on CD38 expression and isatuximab-induced apoptosis, either alone or in combination with IMiDs, were also examined. Moreover, MM cell migration was assessed through CXCR4-mediated assays, and cell adhesion was evaluated via CD49d-dependent assays. Results: Isatuximab and daratumumab did not compete for CD38 binding, confirming distinct epitope recognition. Following depletion with either antibody, CD38 expression on the MM cell surface began to recover within 2 h, suggesting a dynamic regulation of CD38 availability. While daratumumab lacked direct apoptosis, isatuximab induced significant direct cell death. Pomalidomide enhanced isatuximab-induced apoptosis by increasing CD38 expression, whereas lenalidomide had no significant effect. Additionally, both antibodies effectively inhibited MM cell migration and significantly reduced cell adhesion. Conclusions: Their non-competitive binding and shared impact on cell dynamics suggest opportunities for optimizing treatment strategies through combinatorial or sequential approaches in MM therapy.<\/jats:p>","DOI":"10.3390\/pharmaceutics17101278","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T10:54:48Z","timestamp":1759229688000},"page":"1278","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Non-Competitive Binding of Isatuximab and Daratumumab to CD38: Implications for Targeted Therapy in Multiple Myeloma"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2875-4405","authenticated-orcid":false,"given":"Rub\u00e9n","family":"Osuna-G\u00f3mez","sequence":"first","affiliation":[{"name":"Inflammatory Diseases, Institut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"L\u00f3pez-Pardo","sequence":"additional","affiliation":[{"name":"Haematology Department, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3639-3291","authenticated-orcid":false,"given":"Maria","family":"Mulet","sequence":"additional","affiliation":[{"name":"Inflammatory Diseases, Institut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Nomded\u00e9u","sequence":"additional","affiliation":[{"name":"Haematology Department, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabet","family":"Cant\u00f3","sequence":"additional","affiliation":[{"name":"Inflammatory Diseases, Institut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Ortin","sequence":"additional","affiliation":[{"name":"Haematology Department, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngela S\u00e1nchez","family":"Cayuela","sequence":"additional","affiliation":[{"name":"Haematology Department, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1574-9861","authenticated-orcid":false,"given":"Ma \u00c0ngels","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Inflammatory Diseases, Institut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0233-5595","authenticated-orcid":false,"given":"Albert","family":"Guinart-Cuadra","sequence":"additional","affiliation":[{"name":"Inflammatory Diseases, Institut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3909-6682","authenticated-orcid":false,"given":"Silvia","family":"Vidal","sequence":"additional","affiliation":[{"name":"Inflammatory Diseases, Institut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1053\/j.seminoncol.2016.11.004","article-title":"Multiple myeloma epidemiology and survival: A unique malignancy","volume":"43","author":"Kazandjian","year":"2016","journal-title":"Semin. 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