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Searching for the minimum required dose of daratumumab to induce effective plasma cell depletion in antibody-mediated rejection of the kidney graft: a case report.
J Nephrol
January 2025
Renal Transplant Unit, Department of Nephrology and Kidney Transplantation, Hospital Clínic of Barcelona, Carrer Villaroel 170, 08036, Barcelona, Spain.
There is no established treatment for late or chronic antibody-mediated rejection of a kidney graft. Rituximab-based treatment is not effective, since long-lived high-affinity plasma cells do not express CD20 and do not depend on previous maturation steps to generate donor-specific antibodies. Conversely, daratumumab, an anti-CD38 monoclonal antibody, directly targets plasma cells, with proven efficacy in multiple myeloma.
View Article and Find Full Text PDFDelineating MYC-Mediated Escape Mechanisms from Conventional and T Cell-Redirecting Therapeutic Antibodies.
Int J Mol Sci
November 2024
Department of Hematology, Amsterdam UMC Location Vrije Universiteit, 1081 HV Amsterdam, The Netherlands.
In B-cell malignancies, the overexpression of MYC is associated with poor prognosis, but its mechanism underlying resistance to immunochemotherapy remains less clear. In further investigations of this issue, we show here that the pharmacological inhibition of MYC in various lymphoma and multiple myeloma cell lines, as well as patient-derived primary tumor cells, enhances their susceptibility to NK cell-mediated cytotoxicity induced by conventional antibodies targeting CD20 (rituximab) and CD38 (daratumumab), as well as T cell-mediated cytotoxicity induced by the CD19-targeting bispecific T-cell engager blinatumomab. This was associated with upregulation of the target antigen only for rituximab, suggesting additional escape mechanisms.
View Article and Find Full Text PDFPreclinical evaluation of the CD38-targeting engineered toxin body MT-0169 against multiple myeloma.
Hemasphere
November 2024
Amsterdam UMC location Vrije Universiteit Amsterdam, Hematology Amsterdam Netherlands.
Despite significant progress in the treatment of multiple myeloma (MM), relapsed/refractory patients urgently require more effective therapies. We here describe the discovery, mechanism of action, and preclinical anti-MM activity of engineered toxin body MT-0169, a next-generation immunotoxin comprising a CD38-specific antibody fragment linked to a de-immunized Shiga-like toxin A subunit (SLTA) payload. We show that specific binding of MT-0169 to CD38 on MM cell lines triggers rapid internalization of SLTA, causing cell death via irreversible ribosome inhibition, protein synthesis blockade, and caspase 3/7 activation.
View Article and Find Full Text PDFEfficacy of Daratumumab-Based Regimens for Extramedullary Pulmonary Plasmacytoma: A Case Report.
Cancer Rep (Hoboken)
November 2024
Hematology and Transplant Center, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno, Italy.
Introduction: Multiple myeloma (MM) with pulmonary extramedullary disease is rare and usually associated with poor prognosis, and no data on daratumumab-based regimens have been reported yet.
Case Presentation: Here, a 64-year-old man with pulmonary plasmacytoma received daratumumab-based regimens and has achieved a very good partial response with lung mass disappearance and overall survival of 16 months. He did not receive autologous stem cell transplantation because of several comorbidities, such as severe drug-induced neuropathy and JAK2-mutated myeloproliferative neoplasm with marked splenomegaly.
Open-Label Phase 1/2 Study of Daratumumab-Based Desensitization Before Kidney Transplantation.
Kidney Int Rep
November 2024
Universite Paris Est Creteil, INSERM IMRB U955, Créteil, France.
Article Synopsis
- The study assesses the safety and efficacy of the anti-CD38 monoclonal antibody daratumumab for kidney transplant candidates with high panel reactive antibodies.
- In the trial, 23 patients were involved across two phases, with notable mild infusion-related adverse events but no serious complications.
- Results showed significant, temporary reductions in anti-HLA antibodies at 3 months, but most immune markers returned to baseline levels after 12 months, indicating less than 40% of patients had a lasting positive response.
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