Our project provides a brand-new solution for cell therapy of cancer – to deal with free extracellular ligands instead of cell surface antigens, which are obviously difficult to reach because of the barrier of tumour microenvironment.

For clinical application, the STEP system can be used to equip cells for cancer therapy. Stable STEP cell line can be produced with T cells extracted from patients. Then it can be reinfused into the blood to monitor level of target ligand and to produce specific drug in real time (Figure 1). In this way we can release patients from the pain of radiotherapy or chemotherapy, while inhibit tumour development in a more efficient way.
One of the biggest advantage STEP has over other treatments is its modifiable upstream and downstream. For ligand recognition, we’ve already developed STEP for VEGF and for D-Dimer, the former for broad-spectrum scanning for tumour and the latter more specific for NSCLC. Both systems will be ready to use after overall test and optimisation in T cells. Our users can also select one or more tumour marker for a particular cancer type, clone the scFv or other kinds of binding domains to the extracellular domain and test the output. The binding affinity can always be increased, or in some cases decreased, with the help of our user-friendly assistant software and Rosetta. If there’s no sequence of binding domain available, we can also help you design a high-affinity scFv in silico with these softwares (Figure 2). As a result, we can literally achieve recognisation of any customer appointed ligands with our STEP system.
Another superiority of STEP is the tuneable downstream and the changeable reporter. The curve of downstream gene expression can be easily modified either by simply changing a transcription factor, or by altering the binding affinity between the DNA sequence and the transcription factor. The reporter, on the other hand, can be any kind of drugs for unique situations of different patients.

Being a highly modular transducer engineering platform and able to meet needs of various kinds of cancer patients, STEP will definitely be the best choice for cell therapy.