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PI3Kδ activation, IL-6 overexpression, and CD37 loss cause resistance to naratuximab emtansine in lymphomas.
Blood Adv
December 2024
Institute of Oncology Research, Faculty of Biomedical Sciences, Università della Svizzera italiana, Bellinzona, Switzerland.
Article Synopsis
- CD37-targeted therapies, like naratuximab emtansine, have shown promise in treating lymphoma, demonstrating strong anti-tumor activity both alone and when combined with rituximab.
- The study investigated 54 lymphoma models, revealing that the drug's effectiveness varied with CD37 expression and discovered mechanisms of resistance related to genetic changes in cancer cells.
- Notable combinations with other drugs (anti-IL6, PI3Kδ inhibitors, and BCL2 inhibitors) improved the drug's efficacy in resistant lymphoma models, suggesting new treatment strategies for tougher cases.
CD37 in acute myeloid leukemia: a novel surface target for drug delivery.
Blood Adv
January 2025
Comprehensive Cancer Center, The Ohio State University, Columbus, OH.
Acute myeloid leukemia (AML) is the most common and lethal leukemia in adults. AML consists of many genetic subtypes, which limits broad applicability of targeted therapy. We discovered that the hematopoiesis-restricted tetraspanin CD37 is expressed on the majority of primary AML blasts and thus may represent a common therapeutic target for AML regardless of subtype.
View Article and Find Full Text PDFCo-stimulation of CD28/CD40 signaling molecule potentiates CAR-T cell efficacy and stemness.
Mol Ther Oncol
September 2024
Stem Cell Laboratory, Hematology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand.
CD19 chimeric antigen receptor T (CD19CAR-T) cells have achieved promising outcomes in relapsed/refractory B cell malignancies. However, recurrences occur due to the loss of CAR-T cell persistence. We developed dual T/B cell co-stimulatory molecules (CD28 and CD40) in CAR-T cells to enhance intense tumoricidal activity and persistence.
View Article and Find Full Text PDFCD20 expression regulates CD37 levels in B-cell lymphoma - implications for immunotherapies.
Oncoimmunology
June 2024
Department of Immunology, Medical University of Warsaw, Warsaw, Poland.
Rituximab (RTX) plus chemotherapy (R-CHOP) applied as a first-line therapy for lymphoma leads to a relapse in approximately 40% of the patients. Therefore, novel approaches to treat aggressive lymphomas are being intensively investigated. Several RTX-resistant (RR) cell lines have been established as surrogate models to study resistance to R-CHOP.
View Article and Find Full Text PDFPurpose: The transmembrane protein CD37 is expressed almost exclusively in lymphoid tissues, with the highest abundance in mature B cells. CD37-directed antibody- and, more recently, cellular-based approaches have shown preclinical and promising early clinical activity. Naratuximab emtansine (Debio 1562, IMGN529) is an antibodydrug conjugate (ADC) that incorporates an anti-CD37 monoclonal antibody conjugated to the maytansinoid DM1 as payload.
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