CAR T Cells Produced in vivo to Treat Cardiac Injury | Chapter 19 | Diagnostic and Treatment Advances in COVID-19 and SARS-CoV-2

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 delivering modified messenger RNA (mRNA) in T cell–targeted lipid nanoparticles (LNPs). The efficacy of these in vivo–reprogrammed CAR T cells was evaluated by injecting CD5-targeted LNPs into a mouse model of heart failure. Efficient delivery of modified mRNA encoding the CAR to T lymphocytes was observed, which produced transient, effective CAR T cells in vivo. Antifibrotic CAR T cells exhibited trogocytosis and retained the target antigen as they accumulated in the spleen. Treatment with modified mRNA-targeted LNPs reduced fibrosis and restored cardiac function after injury. In vivo generation of CAR T cells may hold promise as a therapeutic platform to treat various diseases.

Author(s) Details:

Joel G. Rurik,
Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA, Penn Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA and Institute for Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

István Tombácz,
Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Amir Yadegari,
Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Pedro O. Méndez Fernández,
Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA, Penn Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA and Institute for Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Swapnil V. Shewale,
Penn Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Li Li,
Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA and Penn Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Toru Kimura,
Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Ousamah Younoss Soliman,
Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Tyler E. Papp,
Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Ying K. Tam,
Acuitas Therapeutics, Vancouver, British Columbia V6T 1Z3, Canada.

Barbara L. Mui,
Acuitas Therapeutics, Vancouver, British Columbia V6T 1Z3, Canada.

Steven M. Albelda,
Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA and Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Ellen Puré,
Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Carl H. June,
Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Haig Aghajanian,
Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA, Penn Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA and Institute for Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Drew Weissman,
Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Hamideh Parhiz,
Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Jonathan A. Epstein,
Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA, Penn Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA and Institute for Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA and Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Please see the link here: https://stm.bookpi.org/DTACSC/article/view/9571