New Method for Detecting Crucial Protein-Protein Interactions Holds Promise for Cancer Immunotherapy

Researchers at the Center for Medical Innovation of Nagasaki University, led by Dr. Hideki Hayashi, have developed a novel system capable of highly sensitive detection of diverse protein-protein interactions. Named "IFNARRS: Interferon α/β Receptor Reconstitution System," this new method opens the door to selecting T cells from cancer patients' blood that specifically recognize cancer cells, activating and proliferating them without genetic modification. This breakthrough holds significant potential for future cancer immunotherapy.

The study detailing this development, titled "Development of a highly sensitive platform for protein-protein interaction detection and regulation of T cell function," is scheduled to be published online in the Proceedings of the National Academy of Sciences (PNAS) during the week of August 5.

https://www.pnas.org/doi/epub/10.1073/pnas.2318190121

In response to viral infections, cells release a protein called interferon α/β (IFNA). This protein is detected by two distinct receptors, IFNAR-1 and IFNAR-2, on the infected and nearby cells, initiating a signaling cascade that helps eliminate the virus. This mechanism is a key example of how protein-protein interactions sustain life by transmitting signals within the body.

The researchers utilized this system to link two proteins X and Y, known to interact, to IFNAR-1 and IFNAR-2, respectively. Upon binding, these proteins triggered a signal within the cells. The IFNARRS system can detect such interactions with unprecedented sensitivity, even converting these signals into other desired signals. This capability allows for the design of targeted signal transduction between cells.

For instance, T cells, which play a crucial role in immune response, can carry receptors that specifically recognize cancer cell antigens. To eliminate cancer cells, these T cells must be activated and proliferated with the help of other immune cells, such as dendritic cells. Using IFNARRS, the researchers created G-188 cells that mimic dendritic cells. These cells detect interferon-gamma (IFNγ) secreted by the patient's own T cells with anticancer activity and respond by expressing genes that activate and proliferate these T cells. This system offers the potential to expand the patient's anticancer T cells outside the body efficiently and reinfuse them for the treatment, presenting a significant advance in cancer immunotherapy.

（insert：August 6, 2024 at 10:00 a.m.)

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