Measuring IL-6 and sIL-6R in serum from patients treated with tocilizumab and/or siltuximab following CAR T cell therapy
| Autor: | Fang Chen, Simon F. Lacey, Noelle V. Frey, Edward Pequignot, Carl H. June, David L. Porter, David T. Teachey, Stephan A. Grupp, Shannon L. Maude, J. Joseph Melenhorst |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Lymphoma medicine.medical_treatment Immunology Receptors Antigen T-Cell Antibodies Monoclonal Humanized Article Siltuximab 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Tocilizumab medicine Humans Immunology and Allergy Molecular Targeted Therapy Interleukin 6 Leukemia biology medicine.diagnostic_test Interleukin-6 business.industry Antibodies Monoclonal Pennsylvania medicine.disease Receptors Interleukin-6 Chimeric antigen receptor Blockade Cytokine release syndrome 030104 developmental biology Cytokine chemistry 030220 oncology & carcinogenesis Immunoassay biology.protein business Signal Transduction |
| Zdroj: | Journal of Immunological Methods. 434:1-8 |
| ISSN: | 0022-1759 |
| DOI: | 10.1016/j.jim.2016.03.005 |
| Popis: | T cells expressing a CD19-specific chimeric antigen receptor (CAR19) are demonstrating remarkable efficacy in hematologic malignancies. Treatment is often associated with life-threatening cytokine release syndrome (CRS) which can be effectively treated with cytokine blockade using the antibodies, Siltuximab or Tocilizumab respectively targeting IL-6 or the IL-6 receptor. As IL-6 blockade is moving into the clinic for the treatment of CRS as well as IL-6-driven rheumatologic and malignant diseases, clinicians are utilizing serum cytokine panels more frequently to assess the effects of IL-6 inhibitors. It is paramount to ascertain whether levels obtained are accurate, especially as certain drugs may, in theory, affect quantification. We report the comparative quantification of IL-6 and sIL-6R using Luminex-based immunoassay kits from two vendors. Our results indicate good agreement of the commercial immunoassays in measurement of IL-6 but disagreement in quantitation of sIL-6R. We found that both Siltuximab and Tocilizumab can interfere with the measurement of their respective ligands using reagents from one vendor but not the second. This has significant implications for the analysis of IL-6 and sIL-6R pharmacokinetics analysis in Siltuximab or Tocilizumab-treated patients. We found that high levels of IL-6 can falsely reduce the measured levels of sIL-6R and high levels of sIL-6R can reduce levels of IL-6 when measured with some commercial assays. These data demonstrate the importance of assessing the impact of cytokine-blocking agents on accuracy of clinical biomarker assays in other diseases, as drugs targeting TNF-alpha, IL1B, and IL5 are being used more frequently in a large number of diseases. |
| Databáze: | OpenAIRE |
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