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

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.