University of Arizona researchers created a new five-module chimeric antigen receptor T cell that has shown potential to fight against Type 1 diabetes.
Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of pancreatic β cells by pathogenic, autoreactive T cells. Effective and safe immunotherapy approaches to treat T1D would enhance personalized medical approaches to mitigate the effects of pathogenic T-cell–mediated diseases such as T1D. A promising approach is the application of chimeric antigen receptor (CAR) T cells, given its known mechanism and current use to treat other diseases such as hematological cancers.
To date, CAR-T therapies to treat cancer have not focused on the molecular signaling and supporting components that drive T-cell function. For this reason, sensitivity is suboptimal, and adverse treatment effects remain to be overcome with the CAR-T technology. T cells function via a multi-component molecular process, a five-module receptor complex composed of a T-cell receptor, three CD3 signaling modules, and a coreceptor. These 5 components or modules work together to achieve the destruction of cells infected with pathogenic antigens.
Scientists from the University of Arizona Health Sciences designed a CAR-T that mimics the 5-module state of T-cells, 5MCar. The biomimetic 5MCar was designed to direct killer T cells to destroy pathogenic autoimmune T cells that cause T1D. This represents a novel immunotherapy approach that functions more closely to T cells’ natural state and function.
The 5MCar cells were tested in a study in experimental T1D mouse models. When the biomimetic cells were adoptively transferred to the mice, the manifestation of T1D was prevented due to targeting of autoimmune CD4+ T cells. The results of the study show that T cells that express 5MCar can effectively destroy pathogenic autoimmune T cells and prevent the development of T1D. Also, the biomimetic design enhances sensitivity and may improve the toxicity profile seen with convention CAR-T designs. Further studies can determine if this approach is a safe and effective immunotherapy for humans with T1D and other aberrant T-cell–induced disorders.
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Genetically Engineered T Cells Could Lead to Therapies for Autoimmune Diseases. (2020). Retrieved 20 January 2021, from https://news.arizona.edu/story/genetically-engineered-t-cells-could-lead-therapies-autoimmune-diseases