While there are a wide variety of current treatments for the cytokine storm, they are typically administered at certain discrete time points, which reduce the ability of clinicians to respond to changes in patient condition. Our proposed treatment adds the element of continuous sensing and allows the treatment to respond to changes in the patient’s condition on short notice. This is particularly important, as the timing of treatments is vital to patient outcomes (Ye et al., 2020). For example, corticosteroids (while an effective treatment) administered at the wrong time of the cytokine storm may delay the clearance of coronavirus due to immunosuppression, leading to delayed recovery. The optimal timing of IFN treatment also remains controversial. Some studies found that IFN treatment before peak viral replication improved mouse survival when infected with SARS-CoV-2, but late IFN administration worsened outcomes and increased viral pathology (Acharya et al., 2020). By having a system where cytokine conditions are continually monitored, our system could help to alleviate the difficulties and dangers of improper treatment timing for patients.
MIT iGEM historically had experience working with HEK293 cells (human embryonic kidney 293 cells), and we were planning on using these cells as our original chassis for initial experimentation. HEK293 cells are useful for experimentation because of their high reproducibility and ease of maintenance; however, HEK293 cells are not suitable for a therapeutic chassis in a therapeutic that could enter a human because they are an immortal cell line. Instead, in the therapeutic stage, we plan on using cells that natively express IP-10 and MCP-3 receptor signaling pathways and thus have the ability to sense and modify the immune response.
Instead, in the therapeutic stage, we plan on using native cells that express IP-10 and MCP-3 receptors and have the capacity to modify the immune response. Using Cell Atlas, we found that the Karpas-707 cell line expressed both these receptors. Karpas-707 is derived from plasma B cells, so a therapeutic chassis could be plasma B cells derived from patients. Additionally, the lifespan and potential immunogenicity of the cells could be improved with alginate encapsulation, in which the cells are delivered in alginate microspheres.
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Ye, Qing et al. “The pathogenesis and treatment of the 'Cytokine Storm' in COVID-19.” The Journal of infection vol. 80,6 (2020): 607-613. doi:10.1016/j.jinf.2020.03.037