ArticleBritish journal of haematology2011
Blockade of interleukin-6 signalling with siltuximab enhances melphalan cytotoxicity in preclinical models of multiple myeloma.
Article in British journal of haematology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 79 citations in OpenAlex.
- Trial
- A phase 2 multicentre study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with relapsed or refractory multiple myeloma.British journal of haematology · 2013Trial
- Genomic profiling enables personalized strategies to overcome drug resistance in multiple myeloma.Discover oncology · 2026Review
- The tumor microenvironment in hematologic malignancies: immune evasion, metabolic reprogramming, and therapeutic resistance.Blood science (Baltimore, Md.) · 2026Review
- Interleukin-6 serves as a critical factor in various cancer progression and therapy.Medical oncology (Northwood, London, England) · 2024Review
- Regulation of Treg cells by cytokine signaling and co-stimulatory molecules.Frontiers in immunology · 2024Review
- Treatment of Multiple Myeloma and the Role of Melphalan in the Era of Modern Therapies-Current Research and Clinical Approaches.Journal of clinical medicine · 2021Review
- Autologous Stem Cell Transplantation for Myeloma: Cytoreduction or an Immunotherapy?Frontiers in immunology · 2021Article
- Review
- Targeting IL-6 receptor reduces IgM levels and tumor growth in Waldenström macroglobulinemia.Oncotarget · 2019Article
- CD38 in Adenosinergic Pathways and Metabolic Re-programming in Human Multiple Myeloma Cells: In-tandem Insights From Basic Science to Therapy.Frontiers in immunology · 2019Review
- Targeting the IL-6/JAK/STAT3 signalling axis in cancer.Nature reviews. Clinical oncology · 2018Review
- Article
- Expression of the IL-6 receptor alpha-chain (CD126) in normal and abnormal plasma cells in monoclonal gammopathy of undetermined significance and smoldering myeloma.Leukemia & lymphoma · 2018Article
- Development of Novel Immunotherapies for Multiple Myeloma.International journal of molecular sciences · 2016Review
- Hormonal-receptor positive breast cancer: IL-6 augments invasion and lymph node metastasis via stimulating cathepsin B expression.Journal of advanced research · 2016Article
- Potential therapeutic implications of IL-6/IL-6R/gp130-targeting agents in breast cancer.Oncotarget · 2016Review
- Monoclonal antibodies in the treatment of multiple myeloma: current status and future perspectives.Leukemia · 2016Review
- The Role of Intracellular Signaling Pathways in the Pathogenesis of Multiple Myeloma and Novel Therapeutic Approaches.Journal of clinical and experimental hematopathology : JCEH · 2016Review
- Immunostimulatory Effects of Melphalan and Usefulness in Adoptive Cell Therapy with Antitumor CD4+ T Cells.Critical reviews in immunology · 2016Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Signalling through the interleukin (IL)-6 pathway induces proliferation and drug resistance of multiple myeloma cells. We therefore sought to determine whether the IL-6-neutralizing monoclonal antibody siltuximab, formerly CNTO 328, could enhance the activity of melphalan, and to examine some of the mechanisms underlying this interaction. Siltuximab increased the cytotoxicity of melphalan in KAS-6/1, INA-6, ANBL-6, and RPMI 8226 human myeloma cell lines (HMCLs) in an additive-to-synergistic manner, and sensitized resistant RPMI 8226.LR5 cells to melphalan. These anti-proliferative effects were accompanied by enhanced activation of drug-specific apoptosis in HMCLs grown in suspension, and in HMCLs co-cultured with a human-derived stromal cell line. Siltuximab with melphalan enhanced activation of caspase-8, caspase-9, and the downstream effector caspase-3 compared with either of the single agents. This increased induction of cell death occurred in association with enhanced Bak activation. Neutralization of IL-6 also suppressed signalling through the phosphoinositide 3-kinase/Akt pathway, as evidenced by decreased phosphorylation of Akt, p70 S6 kinase and 4E-BP1. Importantly, the siltuximab/melphalan regimen demonstrated enhanced anti-proliferative effects against primary plasma cells derived from patients with myeloma, monoclonal gammopathy of undetermined significance, and amyloidosis. These studies provide a rationale for translation of siltuximab into the clinic in combination with melphalan-based therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.