Carnegie Mellon To Develop Molecular Circuit that Acts as Transistor for Immunotherapy

Under a $1 million moonshot grant, Carnegie Mellon University Chemist Danith Ly and colleagues will develop an integrated molecular circuit that will reprogram and redirect the immune system to fight cancer.

The grant is part of an innovative block grant program for the life sciences, funded by a generous $4 million gift from the DSF Charitable Foundation to Carnegie Mellon’s Mellon College of Science. Since the program was established in 2017, it has funded a number of young investigators, early stage research projects and interdisciplinary workshops. This is the first moonshot grant, which supports high-risk, high-reward activities that bring together researchers from different fields to collaborate on a scientifically challenging question. 

The integrated molecular circuit Ly proposes has the potential to revolutionize immuno-oncology much like the invention of transistors did for the field of semi-conductor electronics.

Cancer is known not just for its prevalence but for the devastating side effects of radiation and traditional chemotherapy treatments. And it is hard to treat because the immune system fails to recognize and attack cancer cells. Researchers believe that immunotherapy, which harnesses the immune system to fight cancer cells, is a promising avenue of cancer treatment that could eliminate many of the side effects of traditional therapies.

In one type of immunotherapy called CAR T-cell therapy, immune cells called T-cells are extracted from a patient and modified to produce chimeric antigen receptors (CARs) that can recognize the patient’s tumor cells. The modified T-cells are infused into the patient. They travel through the bloodstream and bind to and kill tumor cells. Disappointingly, early studies of this type of immunotherapy have shown low response rates and high levels of toxic side effects.

“What if, like a transistor, we could dial up or down the chemical signals from CAR T-cells to better control what cells they attack and when?  If we could do this, we could make the treatment more effective and better manage side-effects,” said Ly, who is a professor of chemistry and director of the Institute for Biomedical Design and Discovery at Carnegie Mellon.

With the funding from the DSF Charitable Foundation, Ly and his Carnegie Mellon collaborators Marcel Bruchez, professor of biological sciences and chemistry and director of the Molecular Biosensor and Imaging Center, and Bruce Armitage, professor of chemistry and director of the Center for Nucleic Acids Science and Technology, will create this transistor in the form of an integrated molecular circuit attached to a CAR T-cell (IMC CAR-T). IMC CAR-T will connect a T-cell or natural killer cell to a disease-specific antigen using a nucleic acid recognition element that acts as a universal adapter. The adapter can be activated or deactivated chemically, allowing researchers to modulate the activity of the cells. 

While the researchers are initially developing the IMC CAR-T for cancer immunotherapy, they believe that the system could easily be modified for the rapid mobilization of the immune system to treat a range of diseases, including genetic diseases.

“Treatments using IMC CAR-T have the potential to be safer and more effective than a number of conventional therapies because they are tapping the patient’s own natural therapeutic reserve to fight disease,” said Ly.