The disclosure provides inducible caspase polypeptides, compositions comprising inducible caspase polypeptides and sequences encoding the same, cells modified to express the polypeptides and compositions of the disclosure, as well as methods of making and methods of using same for adoptive cell therapy.

A mesenchymal stem/stromal (MSC) cell line, in particular a human mesenchymal stem cell (hMSC), capable of chondrogenic differentiation when cultured in a chondrogenic medium, comprising a first transgene comprising a first nucleic acid sequence encoding for a preferably mammalian immortalizing enzyme under control of a first promoter sequence operable in said mesenchymal cell and a second transgene comprising a second nucleic acid sequence encoding a preferably mammalian bone morphogenic protein under control of a second promoter sequence operable in said mesenchymal cell.

Described herein are compositions and methods for treating, inhibiting, preventing, reducing the severity of and/or reducing the progression of schwannoma, as well as any disease or physiological disease-state in which schwannoma plays a role. The compositions comprise an rAAV vector that includes a caspase-1 gene or a variant thereof and a Schwann cell specific promoter.

The disclosure provides inducible caspase polypeptides, compositions comprising inducible caspase polypeptides and sequences encoding the same, cells modified to express the polypeptides and compositions of the disclosure, as well as methods of making and methods of using same for adoptive cell therapy.

Up-regulation of caspase has been found in COVID-19 patients, and also occurs in patients suffering from diabetes, hypertension, metabolic syndrome, and other conditions. Such up-regulation can be responsible for poor clinical outcomes in patients having such diseases or disorders, as such up-regulation leads to a process called pyroptosis: death and malfunction of immune system cells, particularly of certain types of lymphocytes. An inhibitor of caspase such as a caspase 1 inhibitor, or pan-caspase inhibitor (i.e., an inhibitor of multiple caspase types including caspase-1), can be used to treat COVID-19 patients or individuals at risk of infection, by limiting the malfunction of the immune system. A caspase-1 or pan-caspase inhibitor is advantageously administered before or very early in the course of infection by a positive-sense, single-stranded RNA virus such as SARS-CoV, MERS-CoV, or SARS-Cov-2.

The disclosure provides inducible caspase polypeptides, compositions comprising inducible caspase polypeptides and sequences encoding the same, cells modified to express the polypeptides and compositions of the disclosure, as well as methods of making and methods of using same for adoptive cell therapy.