“What’s unique about our approach is how the T cell interacts with the antibody. Adding different antibodies, at the same time or one after another, allows the receptor to recognize different tumor features. Via a bio-orthogonal chemistry - a type of reaction that occurs in living systems without interfering with natural processes - the SNAPtag reacts with benzylguanine, fusing the antibody to the receptor. These cells are administered along with cancer-targeting antibodies that are labeled with a molecule called benzylguanine. To overcome this problem, Lohmueller, first author Elisa Ruffo, Ph.D., postdoctoral associate at Pitt, Alexander Deiters, Ph.D., professor of chemistry at Pitt and their colleagues developed universal SNAP-CAR T cells by adding a SNAPtag enzyme to the CAR receptor. “If the tumor evolves to lose that protein or downregulate it, you need to re-engineer the T cells a second time, which is a highly involved and expensive process.” “One of the big problems with CAR T therapy is that you’re targeting just one protein,” explained Lohmueller. “Our hope is that we can use this approach to make cell therapies and deliver genes for cancer, autoimmune disorders, organ transplantation tolerance and more.”ĬAR T cell immunotherapy involves engineering a patient’s own cells so that the T cell receptor recognizes a specific protein on cancer cells before infusing them back into the patient. This SNAP-SynNotch system is super programmable because you can have both designer input and designer gene output,” said senior author Jason Lohmueller, Ph.D., assistant professor of surgery and immunology in the division of surgical oncology at the Pitt School of Medicine and investigator at UPMC Hillman Cancer Center. “We showed for the first time that we can make a universal SynNotch receptor. With the addition of SNAP, the possibilities for customized therapies become almost endless. The researchers showed that their SNAP approach works in two important receptors: CAR receptors, a synthetic T cell receptor that coordinates a suite of immune responses, and SynNotch, a synthetic receptor that can be programmed to activate just about any gene. By tweaking the type or dose of these antibodies, treatments could be tailored for optimal immune responses. The discovery could extend into solid tumors and give more patients access to the game-changing results CAR T cell therapy has produced in certain blood cancers.ĭescribed in a Nature Communications study published today, the new approach involves engineering T cells with receptors bearing a universal “SNAPtag” that fuses with antibodies targeting different proteins. PITTSBURGH - University of Pittsburgh researchers have developed a universal receptor system that allows T cells to recognize any cell surface target, enabling highly customizable CAR T cell and other immunotherapies for treating cancer and other diseases.
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