Fibrosis affects millions of people with cardiac disease. We developed a therapeutic approach to generate transient antifibrotic chimeric antigen receptor (CAR) T cells in vivo by deliverin
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April 10, 2022 8:41 PM
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The standard CAR T cell strategy would be problematic when directed against heart failure or other fibrotic diseases in humans.
Fibroblasts have a normal and important function in the body, particularly in wound healing. CAR T cells that are genetically reprogrammed to attack fibroblasts could survive in the body for months or even years, suppressing the fibroblast population and impairing wound healing for all that time. Therefore, in the new study published in Science, Epstein and colleagues designed a technique for a more temporary and controllable, and much more procedurally simple, type of CAR T cell therapy. They designed an mRNA that encodes a T-cell receptor targeting activated fibroblasts and encapsulated the mRNA in tiny bubble-like lipid nanoparticles, which are themselves coated with molecules that lodge in T cells. Injections of this therapy into mice modeling heart failure successfully reprogrammed a large population of mouse T cells, causing a major reduction in cardiac fibrosis in the animals and restoration of a mostly normal heart size and function with no sign of continued anti-fibroblast T cell activity one week after treatment. Researchers continue to test this mRNA-based transient CAR T-cell technology, with the hope of eventually starting clinical trials