The invention relates to methods of treatment of a solid tumor in a patient in need thereof, comprising administering to the patient: (i) an effective amount of engineered immune cells originating from a donor expressing at their cell surface a Chimeric Antigen Receptor (CAR) directed against Fibroblast Activation Protein (FAP), and (ii) an effective amount of an immunotherapy treatment that elicits an immune response in the patient.

A chimeric polypeptide, containing a binding peptide that can specifically bind to a target molecule, a receptor regulatory domain containing one or more cleavage sites, and an intracellular domain. The receptor regulatory domain comprises an extracellular region and a transmembrane region, wherein the extracellular region and the transmembrane region are not both derived from a Notch protein. The binding of the binding peptide to the target molecule can induce the cleavage of the receptor regulatory domain, thereby releasing the intracellular domain.

Provided are methods for identifying subjects at risk for reduced lifespan, age-associated cardiomyopathy, reduced cardiac function, heart failure, increased fibrosis of the myocardium, lung, and/or kidney; idiopathic pulmonary fibrosis (IPF); elevated left ventricular filling pressure (E/e) indicative of diastolic dysfunction; and/or reduced cognitive function. In some embodiments, the methods include determining if the subject has mosaic loss of chromosome Y in blood (mLOY). Also provided are methods for preventing and/or treating diseases, disorders, and/or conditions associated with mLOY, which in some embodiments also include administering an anti-fibrotic therapy to the subject. Also provided are uses of inhibitors of TGF signaling or senolytic agents for prevention and/or treatment of diseases, disorders, and/or conditions associated with mLOY.

The invention relates to an immune cell engineered to express a chimeric antigen receptor (CAR) which specifically binds Fibroblast Activation Protein (FAP) for use in the treatment of skeletal muscle fibrosis in muscular dystrophies.