ArticleProceedings of the National Academy of Sciences of the United States of America2006
Preclinical and phase I clinical trial of blockade of IL-15 using Mikbeta1 monoclonal antibody in T cell large granular lymphocyte leukemia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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
35 citing papers in PubMed, 67 citations in OpenAlex.
- Computational identification and experimental validation of shared diagnostic biomarkers and gene signatures across HLA-B27-associated immune-mediated diseases.Journal of translational medicine · 2026Article
- Celiac Disease-Narrative Review on Progress in Celiac Disease.Foods (Basel, Switzerland) · 2025Review
- New, Low-Molecular Weight Chemical Compounds Inhibiting Biological Activity of Interleukin 15.Molecules (Basel, Switzerland) · 2023Article
- The role of interleukin-15 in the development and treatment of hematological malignancies.Frontiers in immunology · 2023Review
- Large Granular Lymphocytic Leukemia: Current State of Diagnosis, Pathogenesis and Treatment.Current oncology reports · 2022Review
- Pathogenesis and Treatment of T-Large Granular Lymphocytic Leukemia (T-LGLL) in the Setting of Rheumatic Disease.Frontiers in oncology · 2022Review
- Endogenous memory T cells with donor-reactivity: early post-transplant mediators of acute graft injury in unsensitized recipients.Transplant international : official journal of the European Society for Organ Transplantation · 2021Review
- Results From a First-in-Human Study of BNZ-1, a Selective Multicytokine Inhibitor Targeting Members of the Common Gamma (γc) Family of Cytokines.Journal of clinical pharmacology · 2020Article
- Identification of a γc Receptor Antagonist That Prevents Reprogramming of Human Tissue-resident Cytotoxic T Cells by IL15 and IL21.Gastroenterology · 2020Article
- Interleukin-15 (dys)regulation of lymphoid homeostasis: Implications for therapy of autoimmunity and cancer.The Journal of experimental medicine · 2020Review
- Clinical trial of a humanized anti-IL-2/IL-15 receptor β chain in HAM/TSP.Annals of clinical and translational neurology · 2019Article
- Regulatory T cells limit unconventional memory to preserve the capacity to mount protective CD8 memory responses to pathogens.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Mechanistic Insights into CpG DNA and IL-15 Synergy in Promoting B Cell Chronic Lymphocytic Leukemia Clonal Expansion.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Regulatory effects of IL-15 on allergen-induced airway obstruction.The Journal of allergy and clinical immunology · 2018Article
- CD4 T-cell cytokines synergize to induce proliferation of malignant and nonmalignant innate intraepithelial lymphocytes.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Knowledge-based analysis of genetic associations of rheumatoid arthritis to inform studies searching for pleiotropic genes: a literature review and network analysis.Arthritis research & therapy · 2015Review
- Article
- IL-15-dependent CD8+ CD122+ T cells ameliorate experimental autoimmune encephalomyelitis by modulating IL-17 production by CD4+ T cells.European journal of immunology · 2014Article
- IL-15: a central regulator of celiac disease immunopathology.Immunological reviews · 2014Review
- Molecular pathways: interleukin-15 signaling in health and in cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Twelve patients with T cell large granular lymphocyte leukemia and associated hematocytopenia were treated in a phase I dose-escalation trial with the murine monoclonal antibody Mikbeta1. Mikbeta1 identifies CD122, the beta-subunit shared by the IL-2 and IL-15 receptors. At the doses administered in this study the antibody inhibited the actions of IL-15 on both natural killer and T cells and that of IL-2 when the intermediate-affinity IL-2 receptor was expressed. Mikbeta1 treatment was not associated with significant toxicity or with the development of an immune response to the infused monoclonal antibody. At these doses of Mikbeta1, >95% saturation of the IL-2/IL-15beta receptor (CD122) on the surfaces of the leukemic cells was achieved. Furthermore, in seven patients this led to the down-modulation of the receptor from the surfaces of the leukemic cells. Nevertheless, no patients manifested a reduction in peripheral leukemic cell count or an amelioration of their hematocytopenia. This latter observation may reflect the fact that the monoclonal T cell large granular lymphocyte leukemia leukemic cells of the patients did not produce IL-2 or IL-15 or require their actions for cell survival. In light of the lack of toxicity and lack of immunogenicity of the antibody observed in the present study and the role for IL-15 in the pathogenesis of autoimmune diseases, clinical trials should be performed using the humanized version of Mikbeta1 in groups of patients with human T cell lymphotropic virus I-associated myelopathy/tropical spastic paraparesis, rheumatoid arthritis, multiple sclerosis and refractory celiac disease.
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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.