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Abstract:
A novel immunotherapy strategy using in vivo generation of transient engineered chimeric antigen receptor (CAR) T cells, through the delivery of modified mRNA, can reduce fibrosis and restore cardiac function in a mouse model of heart failure, researchers report.

In vivo generation of engineered CAR T cells can repair a broken heart

Washington, DC | Posted on January 7th, 2022

The findings show that the approach could be useful as a personalized therapeutic platform to treat various other fibrotic diseases or associated disorders. Cardiac fibrosis – the stiffening and scarring of heart tissue following injury – is a hallmark of heart disease and plays a critical role in heart failure and death for millions worldwide. However, therapies targeting cardiac fibrosis remain limited and only demonstrate a modest positive effect at best. Building upon previous research that demonstrated the use of CAR T cells to eliminate activated fibroblasts as a therapy for heart failure, Joel Rurik et al. developed a new approach, which leverages in vivo generation of engineered, transient CAR T cells that selectively recognize and target fibrotic cells in the heart. To do this, Rurik et al. delivered modified mRNA in T cell targeted lipid nanoparticles in a mouse model of heart failure, which reprogrammed T lymphocytes and facilitated the generation of therapeutic CAR T cells entirely within the body. The authors found that the treatment approach successfully reduced fibrosis and restored cardiac function after injury. “This work represents an exciting step toward translating personalized immunotherapies into accessible and affordable ‘off-the-shelf’ engineered T cell products,” write Torahito Gao and Yvonne Chen in a related Perspective.

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Contacts:
Science Press Package Team
American Association for the Advancement of Science/AAAS

Expert Contacts

Haig Aghajanian
Perelman School of Medicine at the University of Pennsylvania

Office: 1-215-820-1942
Drew Weissman
Perelman School of Medicine at the University of Pennsylvania

Hamideh Parhiz
Perelman School of Medicine at the University of Pennsylvania

Office: 1-832-926-3445
Jonathan Epstein
Perelman School of Medicine at the University of Pennsylvania

Cell: 1-215-266-7837
Yvonne Chen
University of California–Los Angeles (UCLA)