Targeting cardiac fibrosis with engineered T cells

Area of Science:

• Cardiology
• Immunology
• Fibrosis Research

Background:

• Cardiac fibrosis, characterized by excess extracellular matrix deposition, stiffens the heart and impairs function.
• It is a key factor in various cardiac diseases and heart failure progression.
• Current therapies targeting cardiac fibrosis are limited.

Purpose of the Study:

• To investigate the efficacy of T cell immunotherapy for targeting pathological cardiac fibrosis.
• To identify and validate a specific cellular target for this immunotherapy.

Main Methods:

• Utilized redirected T cell immunotherapy to target cardiac fibroblasts expressing a xenogeneic antigen in mice.
• Performed gene expression analysis of cardiac fibroblasts from human hearts to identify endogenous targets.
• Developed chimeric antigen receptor T cells targeting fibroblast activation protein (FAP).

Main Results:

• Adoptive transfer of antigen-specific CD8+ T cells successfully ablated cardiac fibroblasts expressing a xenogeneic antigen.
• Fibroblast activation protein (FAP) was identified as an endogenous target on cardiac fibroblasts.
• Chimeric antigen receptor T cell therapy targeting FAP significantly reduced cardiac fibrosis and restored cardiac function post-injury in mice.

Conclusions:

• Redirected T cell immunotherapy demonstrates efficacy in targeting and reducing pathological cardiac fibrosis.
• Fibroblast activation protein (FAP) is a viable target for immunotherapeutic intervention in cardiac fibrosis.
• This study provides proof-of-principle for developing novel immunotherapies for cardiac diseases.