Stacy Matthews Branch, DVM, PhD
Genetically Engineered T Cells May Lead to New Immunotherapy for Diabetes
Researchers create new five-module CAR-T cell that shows potential 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.
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
This article was written by free-lance science writer Stacy Matthews Branch, DVM, PhD. It originally appeared on a blog managed by HemaCare, which Charles River acquired in 2020. HemaCare sells biological products such as T cells, stem cells, bone marrow, plasma, and other medical products. When conducting medical research, you want to have the best products available to you. If you are looking to purchase cellular products, contact HemaCare with any questions you may have.