CAR-T cell (chimeric antigen receptor) therapy has proven to be very successful in hematological cancers such as leukemia. CAR-T therapy consists of drawing the patient’s own T-cells, implanting them with an artificial receptor that recognizes an antigen on the surface of the tumor, multiplying the T-cells in the lab, and re-introducing them into the patient. The T-cells then seek out the tumor using the artificial receptor to bind to and destroy the tumor cell.

However, these engineered T-cells also seek out and kill the patient’s normal cells that express the same antigen. In a Phase I clinical trial, the engineered T-cells were able to kill the tumor cells, but significant adverse effects were observed, owing to “off-tumor” killing of normal tissue cells expressing the target protein that the T-cells recognized.

Pin Wang, is a professor of Chemical Engineering & Materials Science at the University of  Southern California who concentrates his work on the emerging field of “immunobioengineering” whereby he develops immunotherapies to treat metastatic cancers. In FY2016, he received a two-year PRCRP grant to engineer a switchable peptide to reduce the off-target toxicity of CAR-T cell therapy in kidney cancer. He is in the process of developing a peptide[1] that will bind to the artificially-created receptor on the T-cell, which will temporarily prevent the T-cell from binding to both normal and cancer cells. However, when the T-cell is exposed to proteases (enzymes) on the tumor cell, the peptide is synthesized and removed, exposing the artificial receptor, which then destroys the tumor cell. The process reduces toxicity caused by the CAR-T cell while attacking the tumor cells directly and, at the same time, launching an immune response so that cytokines and other immune cells can also assist in killing the tumor cells.

If this “switchable” peptide is successfully developed, which should be known in the next two or three months, work can then proceed on turning it into a therapy that combines with CAR-T to successfully treats kidney cancer metastasis.

[1] A peptide is a small protein, one that has few amino acids in its make-up and limited functions. It can be engineered to bind to the target site.