Reduce CAR-T toxicity! The Nature sub-journal reports on the new safety switch, Hunger Therapy.

In 2017, Novartis's Kymriah was approved by the FDA for the treatment of patients with acute lymphoblastic leukemia (ALL) under the age of 25, the world's first listed CAR-T therapyAfter, competition from drug companies and research institutions over CAR-T has become more intensebut this kind of changed blood cancer treatment cell therapy also has a series of safety problems that need to be solved urgently, cytokine storm is one of themback in 2012, when CAR-T was an experimental therapy, six-year-old Emma Whitehead's leukemia returned, and researchers gave her CAR-T therapyalthough these genetically modified T cells eventually cleared Emma's cancer cells, the resulting inanifit immune response storms nearly took her life, and this is not an exampleAfter, the researchers came up with a number of solutions to this adverse reactionMost of theare attempts to insert a "death switch" into CAR-T cells, a gene that expresses a specific protein, and when a patient is trapped in car-T side effects, it uses small molecules that target the protein to kill The T-cellHowever, it's not so easy to target and kill T-cells, and existing cell therapies that add control switches require new genetic material to be introduced into cells, and immunogenic and genetically modified silence has long plagued researchers, unlike these common plug-in switching solutions to CAR-T toxicity, Dr James Patterson of the University of Cambridge, while studying for a PhD at the Yeast Laboratory at the Francis Crick Institute in London, began thinking about whether a long-used method called nutritional defects used by yeast biologists could be used to address the toxic effects of CAR-T, which is to genetically modify cells to rely on specific nutrients, and then to make them live or die by providing or removing themIn an article published July 13,, in Nature Biotechnology, DrPatterson and a team at Stanford University demonstrated that the concept can work in mice and cell linesteam knocked out the urethra monophosphate synthesis enzyme (UMPS) gene in T-cells and stem cells, which makes cell proliferation dependent on external urethosine, which can be controlled in both in vitro and in the body in heterogeneous transplant models by regulating the supply of urethosinethis approach will increase the safety of cell therapy, making it possible to develop treatments with higher risk, especially those with limited treatment timePhoto Source: Nature Biotechnology Patterson founded Auxolytic based on this approach, working on the development of new safe "off" switches for all types of cellscompany hopes to survive by knocking out specific enzyme genes to make cells dependent on specific nutrients, and in practice, patients take specific nutrients to activate cell activity, and if serious side effects are observed, therapeutic cells in the body can be removed or eliminated, thereby reducing or stopping side effectsPhoto Source: Auxolytic Website Currently, a number of companies have joined the development of CAR-T switches, and pipeline development by companies such as Bellicum Pharmaceuticals, Precigen, Poseida Therapeutics and Autolus Therapeutics focuses on small molecules or engineering protein-induced CAR-T "suicide" pathways, and BioAtla focuses on CAR-T condition activation, with CAB (Biology-T) technology based on tumor micro-environment parametersAuxolytic's next step is to incorporate this distinctive nutritional switching technology into a variety of cell therapies and seek to work with companies that promote breakthrough cell therapies to improve their products and expand the number of patients who can benefit from themReferences: 1- The world's first "CAR-T" therapy has been approved for sale, opening a new chapter in cancer immunotherapy (Source: Tech Guide) 2 s Volker Wiebking, James OPatterson, Renata Martin, et alBlythe Projecting Projects A Transgene-Free Safety Switch for the Switches (Source: Auxolytic)4-Engineering an on/off switch for CAR-T out of yeast and Jurassic Park (Source: EndpointNews)