Dataset Information

Measuring IL-6 and sIL-6R in serum from patients treated with tocilizumab and/or siltuximab following CAR T cell therapy.

ABSTRACT: 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.

SUBMITTER: Chen F

PROVIDER: S-EPMC5490247 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Measuring IL-6 and sIL-6R in serum from patients treated with tocilizumab and/or siltuximab following CAR T cell therapy.

Chen Fang F Teachey David T DT Pequignot Edward E Frey Noelle N Porter David D Maude Shannon L SL Grupp Stephan A SA June Carl H CH Melenhorst Jan J JJ Lacey Simon F SF

Journal of immunological methods 20160403

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 disease ...[more]

PMID: 27049586

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Project description:Prostate cancer (PCa) is a key public health problem worldwide; at diagnosis, a high percentage of patients exhibit tumor cell invasion of adjacent tissue. STAT‑3, IL‑6 receptor (R) and IL‑6 serum levels are associated with enhanced PCa migratory, invasive, clonogenic and metastatic ability. Inhibiting the STAT‑3 pathway at different levels (cytokines, receptors, and kinases) exhibits relative success in cancer. The present study investigated the effect of Stattic (Stt) + Tocilizumab (Tcz) on proliferative, clonogenic, migratory and invasive ability of human metastatic PCa (assessed by colony formation, wound healing and migration assay). RWPE‑1 (epithelial prostate immortalized cells), 22Rv1 (Tumor cells), LNCaP (Metastatic cells) and DU‑145 (metastatic, castration‑resistant prostate cells) cells were used in vitro to evaluate levels of cytokines, chemokines, growth factors (Cytometric Bead Array), STAT‑3, phosphorylated STAT‑3 (In‑Cell Western), IL‑6R, vimentin and epithelial (E‑) cadherin (Western Blot). The effect of inhibition of STAT‑3 (expressed constitutively in DU‑145 cells) with Stt and/or Tcz on expression levels of vimentin, VEGF, and E‑cadherin, as well as proliferative, clonogenic, migratory and invasive capacity of metastatic PCa cells was assessed. The expression levels of IL‑6, C‑X‑C chemokine ligand 8, VEGF and vimentin, as well as proliferation and migration, were increased in metastatic PCa cells. Treatment with Stt or Tcz decreased vimentin and VEGF and increased E‑cadherin expression levels and inhibited proliferative, clonogenic, migratory and invasive capacity of DU‑145 cells; addition of IL‑6 decreased this inhibitory effect. However, Stt + Tcz maintained inhibition even in the present of high concentrations of IL‑6. Stt + Tcz decreased expression of vimentin and VEGF and inhibited the proliferative, clonogenic, migratory and invasive capacity of metastatic PCa cells. To the best of our knowledge, the present study is the first to combine Stt, a STAT‑3 inhibitor, with Tcz, an antibody against IL‑6R, to target tumor cells.

Dataset Information

Measuring IL-6 and sIL-6R in serum from patients treated with tocilizumab and/or siltuximab following CAR T cell therapy.

Publications

Measuring IL-6 and sIL-6R in serum from patients treated with tocilizumab and/or siltuximab following CAR T cell therapy.

Similar Datasets

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