BY Rolf RydahlThis Breakthrough Could Lead to Improved Safety of Cancer-Killing CAR T Cells Through a new device, scientists have been able to identify specific cells which need to be targeted despite them looking nearly identical to neighboring cells. This can help them treat diseased cells, for example, which may only have changed subtly from their original structure -- this being a major cause for concern when trying to safely treat this type of disease. In a recent paper published in Science, a team of researchers at the University of Washington School of Medicine and the Fred Hutchinson Cancer Research Center in Seattle explain how they developed a device made entirely of synthetic proteins that has the capacity to identify, target, and send biological agents to only those cells which express certain combinations of cell surface markers. The outstanding feature of this design is that it operates entirely on its own and can be programmed to a myriad of combinations, making its applications beyond numerous. "We were trying to solve a key problem in medicine, which is how to target specific cells in a complex environment," said Marc Lajoie, a lead author of the study and recent postdoctoral scholar at the UW Medicine Institute for Protein Design. "Unfortunately, most cells lack a single surface marker that is unique to just them. So, to improve cell targeting, we created a way to direct almost any biological function to any cell by going after combinations of cell surface markers." The design is being called Co-LOCKR, or Colocalization-dependant Latching Orthogonal Cage/Key pRoteins. It consists of at least two synthetic proteins -- one Cage and one Key -- but can have additional Keys as well as Decoys. These proteins are used to make boolean logic combinations: whenever a Cage and a Key bind to a cell without a Decoy binding to it as well, the union will activate a signal. When this signal becomes active, it attracts whatever biological activity was predetermined to the cell. To demonstrate this effect, the researchers programmed Co-LOCKR to focus the cell killing of CAR T Cells. The Co-LOCKR was introduced, along with the T Cells, into an amalgam of cells containing one, two or three of the Cage or Key markers, but some of these cells also had Decoy markers which were only found on healthy non-cancerous cells. The T Cells had effectively killed all of the cells with the correct combinations; additionally, those that had the Decoy marker or did not have the correct combination were barely touched. While other methods with similar accuracy involving engineered cells do exist, they take much longer than the Co-LOCKR cell targeting which relies entirely on proteins. "We believe Co-LOCKR will be useful in many areas where precise cell targeting is needed, including immunotherapy and gene therapy," said David Baker, professor of biochemistry at the UW School of Medicine and director of the Institute for Protein Design. And he couldn’t be more right. With its accuracy and speed, Co-LOCKR could be a game changer for the medical field. It has proven in its initial experiments to be able to even target cancer -- the second highest cause of deaths globally. If this tool can show consistent success in future trials and be adapted for use on humans, it will truly be a milestone in the world of medicine. References:
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