Compositions and Methods for Treating Heart Disease via Redirected T Cell Immunotherapies

Abstract

The present invention includes compositions and methods for treating heart disease and/or heart failure. In one embodiment, the treatment includes administering to the subject a cell genetically modified to express a chimeric antigen receptor (CAR), comprising an antigen binding domain specific for fibroblast activation protein (FAP). In another embodiment, the treatment includes administering a cell genetically modified to express a T cell receptor (TCR) specific for an activated fibroblast.

1 . A method for treating heart disease in a subject in need thereof, the method comprising
 administering a cell genetically modified to express a chimeric antigen receptor (CAR) or a T cell receptor (TCR) to the subject, wherein the CAR or the TCR specifically bind to a fibroblast activation protein (FAP), thereby treating the heart disease.   
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the heart disease comprises cardiac fibrosis. 
     
     
         4 . The method of  claim 1 , wherein the cell is a T cell. 
     
     
         5 - 11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein the CAR or the TCR comprises the light and heavy chains of an F19 anti-human FAP monoclonal antibody. 
     
     
         13 . The method of  claim 1 , wherein the CAR or the TCR comprises means for specifically binding the FAP. 
     
     
         14 . The method of  claim 1 , wherein the cell is genetically modified to express the CAR, and wherein the CAR further comprises an intracellular domain comprising a CD28 or 4-1BB signaling domain and a CD3-zeta signaling domain. 
     
     
         15 . The method of  claim 14 , wherein the intracellular domain comprises the 4-1BB signaling domain and the CD3-zeta signaling domain, wherein the 4-1BB signaling domain comprises an amino acid sequence encoded by the nucleic acid sequence comprising SEQ ID NO: 4, and wherein the CD3-zeta signaling domain comprises an amino acid sequence encoded by the nucleic acid sequence comprising SEQ ID NO: 5.