ArticleCancers2021
Co-Stimulatory versus Cell Death Aspects of Agonistic CD40 Monoclonal Antibody Selicrelumab in Chronic Lymphocytic Leukemia.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 8 citations in OpenAlex.
- CD86, the double agent: Significance of CD86 expression in B-cell malignancies.International journal of cancer · 2025Review
- A novel risk score model incorporating six co-stimulatory molecules for accurate prognosis prediction of laryngeal cancer.Translational cancer research · 2025Article
- T-cell dysfunction in CLL is mediated through expression of Siglec-10 ligands CD24 and CD52 on CLL cells.Blood advances · 2024Article
- Treg-selective IL-2 starvation synergizes with CD40 activation to sustain durable responses in lymphoma models.Journal for immunotherapy of cancer · 2023Article
- NF-kB and the CLL microenvironment.Frontiers in oncology · 2023Review
- Enhanced Costimulatory Signaling Improves CAR T-cell Effector Responses in CLL.Cancer research communications · 2022Article
- In Vitro and In Vivo Models of CLL-T Cell Interactions: Implications for Drug Testing.Cancers · 2022Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesChronic lymphocytic leukemia (CLL) is a common form of leukemia with a heterogeneous clinical course that remains incurable due to the development of therapy resistance. In lymph node proliferation centers, signals from the microenvironment such as CD40 ligation through interaction with follicular T helper cells shield CLL cells from apoptosis. Previous observations have shown that, despite CD40-induced changes in apoptotic mediators resulting in cell survival, CD40 activation also increases sensitivity to cell death by CD20 mAbs rituximab and obinutuzumab. To further investigate these observations, we here studied the activity of the fully human agonistic CD40 mAb selicrelumab in primary CLL cells in relation to cell activation, induced pro-survival profile, and sensitization for cell death by aCD20 mAbs, in vitro.
methodsCLL cells from peripheral blood were isolated by the Ficoll density method. The expression of activation markers and cytokine production following CD40 stimulation was quantified by flow cytometry and ELISA. The anti-apoptotic profile of CLL induced by stimulation was evaluated by the expression of BCL-2 proteins with Western blot, and resistance to venetoclax with flow cytometry. Cell death induced by the combination of selicrelumab and aCD20 mAbs was quantified by flow cytometry.
resultsCLL cells treated with selicrelumab upregulated co-stimulatory molecules such as CD86, TNF-α and death receptor CD95/Fas. In contrast to the CD40 ligand-transfected NIH3T3 cells, induction of resistance to venetoclax by selicrelumab was very moderate. Importantly, selicrelumab stimulation positively sensitized CLL cells to CD20-induced cell death, comparable to CD40 ligand-transfected NIH3T3 cells.
conclusionsTaken together, these novel insights into selicrelumab-stimulatory effects in CLL may be considered for developing new therapeutic strategies, particularly in combination with obinutuzumab.
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