Designer molecular mops: Water-soluble cytokine receptors fused with Fc domain of IgG may be therapeutic for cytokine storms

In April 2019, Shuguang Zhang's lab started to use the QTY code to design a class of water-soluble cytokine receptors, including interferon receptors and interleukin receptors, to overcome a major medical problem called a cytokine storm. A cytokine storm is a potentially life-threatening side effect seen in CAR-T (chimera antigen receptor T-cells) treatment of leukemia, lymphoma and perhaps other cancers. Symptoms include fever, fatigue, loss of appetite, muscle and joint pain, nausea, vomiting, diarrhea, rashes, fast breathing, rapid heartbeat, low blood pressure, seizures, headache, confusion, delirium, hallucinations, tremor, and loss of coordination. A cytokine storm is the overreaction of patients' own immune systems that can result in multi-organ failure. COVID-19 is known to cause severe and often fatal cytokine storm in patients with acute infection.

One year ago, Zhang’s lab set out to design a chimera of the water-soluble QTY-variant of cytokine receptors fused with the Fc domain of Immunoglobulin G (IgG). The resulting chimeric cytokine receptors can function as "molecular mops" as they bind with excessive cytokines released in the cytokine storm, thus protecting the patient from multi-organ failure. The development of a broad spectrum of hydrophilic, functional cytokine receptor-IgG compounds may provide significant therapeutic benefits.

Shuguang Zhang has always emphasized asking good questions and pursuing curiosity-driven research. He often quotes Francis Crick: "If you ask big questions, you get big answers.” Such curiosity-driven research again demonstrates that it is very important to ask a big question in order to overcome a major medical problem in clinics, rather than pursuing crisis-driven, reactive research. The research initiated in April 2019 is directly relevant to the treatment of the most severely infected COVID-19 patients. Curiosity-driven, or even proactive research often leads to preparedness which is key to preventing future disasters.