Israeli Researchers Engineer Stronger T Cells in Preclinical Cancer Study
Researchers at Bar Ilan University and the Weizmann Institute of Science have developed a redesigned T cell receptor scaffold that improved the performance of engineered immune cells in laboratory and animal experiments.
The study
The peer reviewed study was published in Science Advances on September 23.
The researchers call the new receptor design SET, short for Structurally Enhanced TCR.
How SET works
T cell receptors allow immune cells to recognize specific targets. One difficulty in engineered T cell therapies is that introduced receptor chains can pair incorrectly or appear inefficiently on the cell surface, weakening the desired immune response.
The Israeli research team used computational protein design to modify the constant region of the receptor while preserving the part responsible for identifying a particular target.
According to the study, SET improved receptor expression, reduced mispairing and produced stronger activation, cytokine production and killing of target cells across six different T cell receptors.
Results in mice
The researchers also tested the approach in mice carrying human tumors.
Bar Ilan's research announcement reported that tumors in animals receiving SET engineered cells were approximately 35 percent smaller than untreated controls after 83 days, while all mice in the SET group remained alive at day 127 compared with fewer than half in the control group.
The approach was tested against several cancer associated targets as well as viral targets.
Limitations
The findings do not establish that SET is safe or effective in people.
This remains preclinical research, and significant questions including manufacturing, off target effects, long term persistence and safety would have to be addressed before any eventual clinical use.
Why the platform approach matters
The significance is instead in the platform approach.
Rather than redesigning an entire therapeutic receptor for every new target, the researchers are investigating whether a stronger common scaffold could improve multiple engineered T cell therapies.
The correct Science Advances DOI is 10.1126/sciadv.aeb9189.
