Self-Adjusting Cytokine Neutralizer Cells as a Closed-Loop Delivery System of Anti-Inflammatory Biologicals,ACS Synthetic Biology

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Self-Adjusting Cytokine Neutralizer Cells as a Closed-Loop Delivery System of Anti-Inflammatory Biologicals
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2018-10-25 00:00:00 , DOI: 10.1021/acssynbio.8b00113
Dennis Hell ₁

Affiliation

The cytokines tumor necrosis factor α (TNFα) and interleukin 1 β (IL-1β) are both strong NF-κB activators and some of the first cytokines to be released in an inflammatory process. TNFα and IL-1β are present in many autoimmune diseases, such as rheumatoid arthritis (RA). TNFα and IL-1β-blocking therapies are quite successful and established in the treatment of RA, but may also be promising in other diseases. For the treatment of recurring autoimmune diseases, strong controlled sensor-effector cells inhibiting TNFα or IL-1β appear highly predestined. Such cells detect a disease biomarker and autonomously react with the dose-dependent production of therapeutic proteins. Hence, we aim to harness and assemble the interactions of TNFα, IL-1β, and NF-κB, which are an ideal match for synthetic biology-based circuits to rewire the transmission to approved TNFα- or IL-1β-blocking biologicals. Considering the high impact of environmental influences on the dynamics of cell-based systems, we established closed-loop controllable cytokine neutralizer cells, monitoring cytokine levels and autonomously delivering powerful biologicals. This real-time processing system may provide dose-dependent drug delivery, which may be tailored for prospective cell and gene therapies against RA, and may offer a more personalized medicine than calculated drug dosing based on body weight.

中文翻译：

自调节细胞因子中和细胞作为抗炎生物的闭环传递系统

细胞因子肿瘤坏死因子α（TNFα）和白介素1β（IL-1β）都是强大的NF-κB激活剂，并且是在炎症过程中释放的首批细胞因子。TNFα和IL-1β存在于许多自身免疫性疾病中，例如类风湿关节炎（RA）。TNFα和IL-1β阻滞疗法在RA的治疗中非常成功并已确立，但在其他疾病中也可能有希望。对于复发性自身免疫疾病的治疗，抑制TNFα或IL-1β的强烈受控制的传感器效应细胞看来是注定的。这样的细胞检测疾病的生物标志物并自主地与剂量依赖性的治疗蛋白产生反应。因此，我们旨在利用和组装TNFα，IL-1β和NF-κB的相互作用，这是基于合成生物学电路将传输重新连接至批准的TNFα或IL-1β阻断生物学的理想选择。考虑到环境影响对基于细胞的系统动力学的巨大影响，我们建立了闭环可控细胞因子中和细胞，监测细胞因子水平并自主提供功能强大的生物。该实时处理系统可以提供剂量依赖性的药物递送，其可以针对针对RA的前瞻性细胞和基因疗法而定制，并且可以提供比根据体重计算出的药物剂量更个性化的药物。监测细胞因子水平并自主提供功能强大的生物制剂。该实时处理系统可以提供剂量依赖性的药物递送，其可以针对针对RA的前瞻性细胞和基因疗法而定制，并且可以提供比根据体重计算出的药物剂量更个性化的药物。监测细胞因子水平并自主提供功能强大的生物制剂。该实时处理系统可以提供剂量依赖性的药物递送，其可以针对针对RA的前瞻性细胞和基因疗法而定制，并且可以提供比根据体重计算出的药物剂量更个性化的药物。

更新日期：2018-10-25

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