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CAR-T Therapy Involves mRNA Injection That Works Like a Vaccine

Jacob David by Jacob David
July 29, 2022
in Technology
CAR-T Therapy Involves mRNA Injection That Works Like a Vaccine
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Researchers based out of the Perelman School of Medicine at the University of Pennsylvania are reporting success with a new kind of immunotherapy that helps to transform a patient’s immune system cells to focus on heart fibroblast cells. It’s a new approach to immunotherapy based on CAR-T therapy.

CAR-T Therapy at the University of Pennsylvania

With CAR-T therapy (short for “chimeric antigen receptor-based therapy”), scientists will take blood from a patient and then remove T cells from the sample. They augment the patient’s T cells so they have chimeric antigen receptors on their exterior. These CAR-T cells can identify a problematic cell, such as a rogue cancer cell, and then put it out of commission.

The University of Pennsylvania team published a report on their work in a recent issue of Science. They explained that their approach involves having an mRNA preparation that programs a patient’s T cells to focus on heart fibroblast cells. Scientists are interested in heart fibroblast cells since they can be a major factor in patients’ hearts’ failing. Fibroblast cells can make too much fibrous material, causing the heart to function poorly as its muscle stiffens. To counter this fibrosis, scientists have tested altered T cells in laboratory mice that have heart failure. They showed that the new CAR-T therapy approach can reduce the level of fibrosis in heart tissue.

The report’s senior author Jonathan A. Epstein, MD, is chief scientific officer for Penn Medicine and executive vice dean and the William Wikoff Smith Professor of Cardiovascular Research in the Perelman School of Medicine.

He noted that the experimental results have implications beyond heart fibrosis, explaining that “fibrosis underlies many serious disorders, including heart failure, liver disease, and kidney failure, and this technology could turn out to be a scalable and affordable way to address an enormous medical burden.” What’s particularly noteworthy is that it gives scientists the capacity to alter T cells for use in specific applications for disease in a clinical setting, without having to take cells from a patient’s body first.

New Approach with mRNA Vaccine Preparation to Reprogram a Patient’s T Cells

Because Epstein and colleagues at the University of Pennsylvania knew that fibroblasts play an important role in healing wounds and are a normal and desirable part of the heart, they didn’t want to use CAR-T to alter the cells to the point that they could persist for years inside the patient’s body. It wouldn’t be a good idea to allow the modified cells to attack fibroblasts for years to come.

Instead, the researchers designed mRNA that “encodes a T-cell receptor targeting activated fibroblasts and encapsulated the mRNA within tiny, bubble-like lipid nanoparticles (LNPs) that are themselves covered in molecules that home in on T cells.” This is based on the same kind of technology that scientists have used to create vaccines against the COVID-19 novel coronavirus pandemic.

So instead of harvesting a patient’s T cells outside the body and then reinfusing them to combat heart failure, they are injecting the mRNA like a vaccine to reprogram T cells so their function changes temporarily. This allows the body to avoid fibroblast formation to lead to heart failure only for the immediate therapeutic period, while leaving the fibroblasts free to conduct their normal work going forward.

Work Continues at The University of Pennsylvania on mRNA-Based CAR-T Cell Therapy

With the initial success in reprogramming T cells with the injected mRNA, the scientists at the University of Pennsylvania are going to press on with their experiments, with the goal to begin clinical trials at some unspecified date in the future.

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