ArticleLupus science & medicine2016
Inducible T-cell co-stimulator ligand (ICOSL) blockade leads to selective inhibition of anti-KLH IgG responses in subjects with systemic lupus erythematosus.
Article in Lupus science & medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 39 papers, 3 of them syntheses that pooled it.
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.
A Randomized, Double-blind, Placebo-controlled, Ascending, Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 557 in Subjects With Systemic Lupus Erythematosus
Randomized, Multicenter, Double-Blind, Placebo-Controlled, Rising Single Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 557 in Subjects With Systemic Lupus Erythematosus
Who cites it
39 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- In vivo human keyhole limpet hemocyanin challenge in early phase drug development: A systematic review.Clinical and translational science · 2023Pooled it
- In or out of control: Modulating regulatory T cell homeostasis and function with immune checkpoint pathways.Frontiers in immunology · 2022Pooled it
- A Comprehensive Review of Biological Agents for Lupus: Beyond Single Target.Frontiers in immunology · 2020Pooled it
- First-in-human study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of ALPN-101, a dual CD28/ICOS antagonist, in healthy adult subjects.Clinical and translational science · 2021Trial
- Brief Report: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Multiple-Dose Study to Evaluate AMG 557 in Patients With Systemic Lupus Erythematosus and Active Lupus Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2018Trial
- Integrating human plasma proteomes with genome-wide association data implicates novel proteins and drug targets for rheumatoid arthritis.Clinical proteomics · 2026Article
- Inducible T-Cell Co-Stimulator (ICOS) and ICOS Ligand: Dealing With a Two-Faced Cancer Immunoregulatory System.Cancer medicine · 2026Review
- Immune checkpoint imbalance in ANCA-associated vasculitis: insights into disease activity and precision immunotherapy.Frontiers in medicine · 2026Review
- CD28 and ICOS in immune regulation: Structural insights and therapeutic targeting.Bioorganic & medicinal chemistry letters · 2025Review
- Enhancing the treatment potential of IL-17 antagonism in lupus nephritis: finding the right partner.Frontiers in immunology · 2025Review
- High dimensional proteomic mapping of bone marrow immune characteristics in immune thrombocytopenia.Science China. Life sciences · 2024Article
- Interruption of the intratumor CD8Cancer cell · 2024Article
- Pathogenic roles of follicular helper T cells in IgG4-related disease and implications for potential therapy.Frontiers in immunology · 2024Review
- Targeting immune checkpoints in anti-neutrophil cytoplasmic antibodies associated vasculitis: the potential therapeutic targets in the future.Frontiers in immunology · 2023Review
- Article
- Activation Markers on B and T Cells and Immune Checkpoints in Autoimmune Rheumatic Diseases.International journal of molecular sciences · 2022Review
- The immune checkpoint ICOSLG is a relapse-predicting biomarker and therapeutic target in infant t(4;11) acute lymphoblastic leukemia.iScience · 2022Article
- Targeted Therapy of B7 Family Checkpoints as an Innovative Approach to Overcome Cancer Therapy Resistance: A Review from Chemotherapy to Immunotherapy.Molecules (Basel, Switzerland) · 2022Review
- Inducible Costimulator-C-X-C Motif Chemokine Receptor 3 Signaling is Involved in Chronic Obstructive Pulmonary Disease Pathogenesis.International journal of chronic obstructive pulmonary disease · 2022Article
- IGF1R signalling is a guardian of self-tolerance restricting autoantibody production.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesTo evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single-dose and multiple-dose administration of AMG 557, a human anti-inducible T cell co-stimulator ligand (ICOSL) monoclonal antibody, in subjects with systemic lupus erythematosus (SLE).
methodsPatients with mild, stable SLE (n=112) were enrolled in two clinical trials to evaluate the effects of single (1.8-210 mg subcutaneous or 18 mg intravenous) and multiple (6 -210 mg subcutaneous every other week (Q2W)×7) doses of AMG 557. Subjects received two 1 mg intradermal injections 28 days apart of keyhole limpet haemocyanin (KLH), a neoantigen, to assess PD effects of AMG 557. Safety, PK, target occupancy, anti-KLH antibody responses, lymphocyte subset analyses and SLE-associated biomarkers and clinical outcomes were assessed.
resultsAMG 557 demonstrated an acceptable safety profile. The PK properties were consistent with an antibody directed against a cell surface target, with non-linear PK observed at lower concentrations and linear PK at higher concentrations. Target occupancy by AMG 557 was dose dependent and reversible, and maximal occupancy was achieved in the setting of this trial. Anti-AMG 557 antibodies were observed, but none were neutralising and without impact on drug levels. A significant reduction in the anti-KLH IgG response was observed with AMG 557 administration without discernible changes in the anti-KLH IgM response or on the overall IgG levels. No discernible changes were seen in lymphocyte subsets or in SLE-related biomarkers and clinical measures.
conclusionsThe selective reduction in anti-KLH IgG demonstrates a PD effect of AMG 557 in subjects with SLE consistent with the biology of the ICOS pathway and supports further studies of AMG 557 as a potential therapeutic for autoimmune diseases. TRIAL REGISTRATION NUMBERS: NCT02391259 and NCT00774943.
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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.