A Korean research team has developed antibody technology that allows immune cells to precisely control when and where they attack cancer cells. The technology is engineered so that antibodies recognize targets on cancer cell surfaces only in the presence of light or specific chemicals, functioning as a kind of "switch" that operates only at the necessary moment.
KAIST announced on the 27th that a research team led by Heo Won-do, a distinguished professor at the Department of Biological Sciences, has developed the "ExtraBody" platform, which can regulate extracellular target recognition using light and chemical stimuli. The team demonstrated that the technology enables immune cells to react with target cells, such as cancer cells, only at desired moments.
CAR-T therapy is a cell-based treatment in which T cells, the immune cells in the human body, are equipped with an "artificial antenna" to detect cancer cells and then reintroduced into the patient. While it has shown effectiveness in treating certain blood cancers due to its strong ability to attack cancer cells, its limitations include the potential for excessive immune cell activation and attacks on normal cells.
To overcome these limitations of CAR-T therapy, the researchers split antibodies into two fragments and designed them to recombine only in the presence of external stimuli. Antibodies are proteins that recognize and bind to specific targets in the body, such as viruses or cancer cells. While ordinary antibodies bind to their targets immediately upon formation, the team engineered the two fragments to reunite and recognize targets only when light or specific chemicals are present. If conventional antibodies are devices that are always on, ExtraBody is an "on-demand antibody" that activates only when needed.
In their experiments, the team created systems that respond to light and to chemicals separately. They confirmed that the technology can be applied not only to fluorescent proteins but also to EGFR and HER2 proteins, which appear frequently on cancer cell surfaces. The experiments showed that, as intended, the antibodies selectively bound to targets only when external stimuli were present, and the same principle worked across multiple types of antibodies. This indicates that ExtraBody is a platform technology that can be expanded to various cancer targets and antibody formats.
ExtraBody also goes beyond simply recognizing targets and can regulate cell-to-cell interactions. When light was applied, cells made contact with each other and exchanged target proteins, while such reactions barely occurred without light stimulation. The process by which target proteins are delivered into cells was also observed, suggesting potential applications in future research on intercellular signaling.
The team also applied ExtraBody to the synNotch and CAR systems. SynNotch is an "artificial switch receptor" designed to turn on intracellular reactions only when it detects a specific target. The CAR system is an artificial receptor technology that enables immune cells to identify and attack cancer cells. By combining ExtraBody with these systems, the researchers implemented a "dual lock" mechanism in which intracellular signals turn on only when both light and target are simultaneously present, enabling precise control of gene expression, cytokine secretion, and immune cell activation.
The team expects this technology to serve as a new strategy for reducing unintended immune activation and side effects, which have been pointed out as problems in existing CAR-T cell therapy. "This research is a new platform technology that can precisely control cell target recognition at desired times and locations using external stimuli," Distinguished Professor Heo Won-do said. "It can be used as a key foundational technology to enhance the safety and precision of next-generation immunotherapy and cell-based therapeutic technologies."
