Innovative Synthetic Protein Targets and Removes Harmful Cells, Offering New Hope for Cancer and Autoimmune Disorders

Scientists at Kyoto University's Institute for Integrated Cell-Material Sciences (iCeMS) have developed an advanced protein-based therapeutic technology known as Crunch, short for Connector for Removal of Unwanted Cell Habitat. This groundbreaking tool leverages the body's existing waste disposal system to selectively identify and eliminate specific harmful or unnecessary cells, presenting promising implications for treating cancers, autoimmune diseases, and other conditions involving detrimental cell activity.

Under normal circumstances, the body steadily replaces billions of its cells daily, with immune cells called phagocytes playing a critical role in clearing away dying cells through a process called phagocytosis or efferocytosis. These immune cells detect a signal called "eat me" on the surface of dead cells, prompting them to engulf and digest these cells efficiently.

The research team, led by first author Mr. Yuki Yamato, has ingeniously repurposed this natural clearance mechanism. By modifying a protein known as protein S— which naturally assists phagocytes in recognizing dead cells—they engineered Crunch to target living cells that should be removed, such as cancer cells or overactive immune cells in autoimmune disorders. Instead of binding to dead cells, Crunch is designed to identify specific surface proteins unique to unwanted cells.

The process involves replacing the part of protein S responsible for detecting dying cells with custom sensors that recognize surface markers characteristic of targeted harmful cells. When Crunch attaches to its chosen cell, it effectively tags it for removal, convincing phagocytes that the cell is ready for clearance. Importantly, Crunch doesn't physically destroy the cells; it acts as a precise delivery system, marking them for the immune system to eliminate naturally.

Professor Jun Suzuki, the study’s lead researcher, describes their testing of this system in mice. They successfully used Crunch to eradicate cancer cells engineered to express specific surface proteins, as well as to eliminate certain immune cells in a lupus model—both outcomes resulted in a reduction of disease signs.

This innovative approach holds significant potential to complement or surpass existing therapies such as CAR-T cell therapy or antibody treatments, which often involve complex procedures like cell extraction, modification, and reinfusion. Crunch, as a protein-based therapy, could be administered through simple injections, making the treatment more accessible and less invasive.

Furthermore, the modular design of Crunch allows for customization, where targeting sensors can be adapted depending on the disease’s specifics. As Professor Suzuki emphasizes, this platform could serve as a versatile therapeutic ecosystem, incorporating sensors from various sources like antibodies or CAR-T cells.

The research team is now focused on improving Crunch's safety, manufacturing efficiency, and effectiveness in clinical settings. As it advances, this technology could usher in a new era of precision medicine, enabling the immune system to naturally and selectively remove harmful cells, thus opening new avenues in disease treatment.