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首页> 外文期刊>Cytokine >Response to the Letter to the Editor by Susan Thorpe et al.: How predictive are in vitro assays for cytokine release syndrome in vivo? A comparison of methods reveals worrying differences in sensitivity and frequency of response
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Response to the Letter to the Editor by Susan Thorpe et al.: How predictive are in vitro assays for cytokine release syndrome in vivo? A comparison of methods reveals worrying differences in sensitivity and frequency of response

机译：Susan Thorpe等人对《致编辑的信》的回应：体内细胞因子释放综合征的体外测定有多大预测价值？方法的比较表明，敏感性和响应频率存在令人担忧的差异

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To the Editor,We would like to thank Thorpe et al. for their comments on our recently published paper and fully agree that these important points should be considered for every assay format in development for cytokine release hazard identification. Thorpe et al. express their concerns about the sensitivity of the published whole blood assay and consequently about its suitability to predict cytokine release in vivo. This conclusion appears to be mainly based on a comparative plot of absolute concentration results in response to TGN1412 for individual cytokines as detected in the reported clinical trial and in the different in vitro assay formats. Our choice of depicting data includes what we feel reflects all relevant aspects needed for interpretation, since the in vitro background responses and, more importantly, responses to matched isotype controls of different assay formats are known to show large variability. Additionally, from our own experience, absolute cytokine quantification results are affected by the use of different cytokine detection methods. Therefore both background responses in medium and a matched isotype control are critical as the response ratios are usually relatively constant. The ideal control would be an isotype control with the closest possible sequence and structure to the test antibody, which is not able to recognize a human target. While this is the procedure we follow for hazard identification of new drugs, publications in the area frequently do not include such controls, since they are mostly unavailable, and therefore we chose Tysabri as an IgG4-matched control for our TGN1412L investigation as used in other published studies.
机译：对于编辑，我们要感谢索普等人。对于他们在我们最近发表的论文中的评论，并完全同意在开发细胞因子释放危险性鉴定的每种测定形式中都应考虑这些重要点。索普等。表示他们对已发表的全血检测的敏感性以及因此对预测体内细胞因子释放的适用性的担忧。该结论似乎主要基于比较的绝对浓度结果的比较图，该绝对浓度结果是针对已报道的临床试验和不同体外试验形式中检测到的每种细胞因子对TGN1412的响应。我们选择描绘数据的方式包括我们认为反映了解释所需的所有相关方面，因为已知体外背景响应，更重要的是，对不同测定形式的匹配同型对照的响应显示出较大的变异性。此外，根据我们自己的经验，绝对的细胞因子定量结果会受到使用不同细胞因子检测方法的影响。因此，由于反应率通常相对恒定，因此中等和匹配同型对照中的背景响应都是至关重要的。理想的对照将是具有与测试抗体最接近的序列和结构的同种型对照，其不能识别人靶标。尽管这是我们用于识别新药的危险的步骤，但该地区的出版物通常不包含此类对照，因为它们几乎不可用，因此我们选择Tysabri作为TGN1412L研究中与IgG4匹配的对照，用于其他发表的研究。

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