Motivation: Can we reach a close marriage of diagnosis and therapeutics?
Dynamic monitoring of medical conditions is very meaningful for a disease’s management, especially for chronic diseases such as malignant cancer, which is heterogeneous and is constantly changing. As students of a medical university, we are especially interested in cell therapy which is a very promising approach in cancer treatment and has received a lot of success. However, dynamic monitoring of response of cell therapy as well as traditional remedies has remained a challenge. Disease monitoring using CT imaging is the current clinical practice for assessing response to targeted therapy, yet this approach does not fully represent the molecular and pathologic changes occurring in tumors during therapy. Repeat tissue biopsies of accessible cancer lesions have been used to provide insights into therapeutic decision-making but rarely capture the complexity of tumor heterogeneity and are invasive procedures with potential complications. Current liquid biopsies are sometimes not accurate and sensitive enough because of the low concentrations of the biomarkers. And the acknowledged biomarkers in blood are limited to this date.
So, it comes to us that whether we can combine diagnostic and therapeutic capabilities into a single device. We hope that a close marriage of diagnosis and therapeutics could provide therapies that are more specific to individuals and, therefore, more likely to offer improved prognoses.
Our inspiration: What other people have done?
Synthetic Biology in disease diagnosis
Development of synthetic receptors
Synthetic receptors that respond to extracellular inputs in a predictable manner is very important for disease detection. Indeed, the field of programmable receptor engineering has evolved rapidly. Chimeric antigen receptors (CARs), G-protein coupled receptors (GPCRs), synNotch[8-10], MESA, and GEMS are just some of the examples. The most well-known receptor among them perhaps is CAR, which is used in CAR-T and CAR-NK therapies. The synNotch receptors are more generalized than CARs since their intracellular domain can be customized as well as their extracellular scFV domain. However, it can only detect immobilized targets whereas MESA and GEMS can respond to soluble cues.
This year, our aim is to develop a cell-based Theranostic system which is able to monitor cancer as well as combat it. The system has a core device and a monitoring device. The core device is a population of engineered NK cells, which can respond rapidly to transformed and stressed cells and have the intrinsic potential to extravasate and reach their targets in almost all body tissues. Just as the strategy that has been mentioned above, cells of the core device work like guards that patrol a patient’s body. Once they discover their enemies—cancer cells, they will attack the enemies and send out alarm signals. Thus, the biomarkers that are immobilized and deep inside a patient’s body will be transformed into a soluble form in bloodstream and will be received by the monitoring device.
The monitoring device is a group of designer cells that will be microencapsulated and implanted subcutaneously. Just like the biomedical tattoo cells, the monitoring device will form a small pattern and visualize the disease conditions.
With our Theranostic system—Wukong, we hope we could provide patients with more individualized and specific therapies in the fight of cancer, and ultimately improve patient outcomes.
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