In our human immune system, T cells are like a "special force" that protects health and are responsible for performing "safety checks" on cells throughout the body. The T cell receptor (TCR) molecule on the surface of T cells is the core "security detector" that performs the task. Scientists have selected models that can accurately identify cancer cells from numerous TCR molecular "security detectors" and "assembled" them onto cancer patients' T cells, allowing the immune system to accurately target and eliminate cancer cells.
However, the "recognition sensitivity" of natural TCR molecules is limited, and some cunning cancer cells may slip through the net! In response to this problem, Zhao Xiang's research team and collaborators from the Center for Excellence in Molecular Cell Science (Institute of Biochemistry and Cell Biology) of the Chinese Academy of Sciences developed a "histidine scanning method" that can quickly locate the "key sites" in TCR molecules responsible for identifying cancer cells and initiating the clearance process.
After "modifying and upgrading" these sites, the TCR molecules are transformed into highly sensitive and enhanced "security detectors", significantly improving the ability of T cells to eliminate cancer cells. This strategy has shown good anti-cancer effects in mouse experiments, and the relevant research results were published online in the international academic journal "Cell" on February 19, Beijing time.
So, how does this "security check" system work?
Researcher Zhao Xiang of the Center of Excellence for Molecular Cells explained that when the TCR molecule "security detector" works, the cell will present its "identity certificate" – pMHC antigen molecule for inspection. Once the pMHC antigen molecule unique to cancer cells is recognized, the T cells will "catch" it red-handed. This study revealed that histidine can accurately locate the "key button" site where TCR molecules recognize cancer cells and initiate the cancer cell clearance process, and can strengthen the "reverse lock" structure between TCR molecules and pMHC antigen molecules. This not only helps T cells control cancer cells more firmly, but also buys valuable time for T cells to fully activate and initiate the killing process, effectively preventing cancer cells from escaping.
What's more worth mentioning is that this method does not rely on the three-dimensional structural information of TCR molecules. Simply by synchronously modifying multiple selected "key buttons", the ability of TCR molecules to "grab" cancer cells can be enhanced, thereby turning T cells into "super guardians" with superior efficiency. The modified T cells have a higher activation level, stronger lethality, and can accurately distinguish between friend and foe, avoiding accidental damage to healthy cells.
At present, this research has remarkable efficacy in animal models, providing a new idea for the development of a new generation of efficient and precise cancer immunotherapy.
It is worth mentioning that this is the second high-level research published by the Center of Molecular and Cellular Excellence in a top academic journal within 7 days.
