Targeting Cardiac Fibrosis with Engineered T cells

By H. Aghajanian, Toru Kimura, J. Rurik, Aidan S. Hancock, M. Leibowitz, Li Li, J. Scholler, James Monslow, Albert C. Lo, Weiyue Han and 15 more. Nature, 2019

650 citations recorded by the source corpus.

Fibrosis is observed in nearly every form of myocardial disease1. Upon injury, cardiac fibroblasts in the heart begin to remodel the myocardium by depositing excess extracellular matrix, resulting in increased stiffness and reduced compliance of the tissue. Excessive cardiac fibrosis is an important factor in the progression of various forms of cardiac disease and heart failure2. However, clinical interventions and therapies that target fibrosis remain limited3. Here we demonstrate the efficacy of redirected T cell immunotherapy to specifically target pathological cardiac fibrosis in mice. We find that cardiac fibroblasts that express a xenogeneic antigen can be effectively targeted and ablated by adoptive transfer of antigen-specific CD8+ T cells. Through expression analysis of the gene signatures of cardiac fibroblasts obtained from healthy and diseased human hearts, we identify an endogenous target of cardiac fibroblasts—fibroblast activation protein. Adoptive transfer of T cells that express a chimeric antigen receptor against fibroblast activation protein results in a significant reduction in cardiac fibrosis and restoration of function after injury in mice. These results provide proof-of-principle for the development of immunotherapeutic drugs for the treatment of cardiac disease. Adoptive transfer of CAR T cells against the fibroblast marker FAP reduces cardiac fibrosis and restores function after cardiac injury in mice, providing proof-of-principle for the development of immunotherapeutic treatments for cardiac disease.

Subfields: Cardiology and Cardiovascular Medicine, Electrical and Electronic Engineering, Oncology

View Paper: https://www.semanticscholar.org/paper/7051917ad1814c0f9b88b0797511a18a6bb2e48c

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  1. Yanan Wang
  2. Wanying Zhang
  3. He Huang
  4. Xia Li
  5. Chentao Li
  6. P. Qian

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