The sentiment around immunotherapies is optimistic, though finding tumor-specific antigens for immuno-onocology treatments to target has shown to be difficult. Despite some success in some of the tests, these treatments only produce responses in small amounts of patients. So there are a number of efforts in effect to help enhance immuno-oncology techniques. Scientists at the Massachusetts Institute of Technology (MIT) feel they have discovered a way to pin point cancer cells more precisely and stimulate the immune system more perfectly.
The new approach—a gene circuit encoded in DNA—is derived by a concept used in electronics known as “AND gates.” The idea is that only when two inputs are present will the system be changed on and produce an output. To translate it into oncology: The therapy will only activate when two cancer-specific biomarkers are sensed.
It’s important to add this isn’t just another combination therapy. With a regular combination treatment, each part of the drug could potentially work respectively, stimulating different areas of the immune system to generate a systemic response.
By using the AND gate, the result is “much more specific, targeted immunotherapies that work locally at the tumor site” folded into a single package, which can at the same time “stimulate the immune system in multiple different ways,” stated Prof. Timothy Lu, head of the Synthetic Biology Group in MIT’s Research Laboratory of Electronics.
Lu and his team at the university developed artificial markers, or “promoters,” encoded them into the circuit, and delivered them to cells in the affected body area using a virus. The promoters attach to certain proteins in tumor cells, and then activate the circuit to prompt proteins that direct the immune system to eliminate the cells, and a checkpoint inhibitor that takes off the brakes off T-cell activity.
The circuit can be personalized to a variety of tumors. In that case the researchers, supported by the results, anticipate to test the therapy in different cancer models and to develop a delivery system that’s adaptable and easy to manufacture and use. They also look to expand the use of the method to treat autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease.