Abstract: Provided herein are tumor-infiltrating lymphocytes (TILs) engineered to express a membrane-bound interleukin 15 (mbIL15). The mbIL15 TILs can be expanded in vitro using arapid expansion protocol without the use of exogenous interleukin 2 (IL2) and can be used in adoptive cell therapy without concomitant use of an exogenous cytokine such as IL2. The TIL can be further engineered such that the mbIL15 is operably linked to one or more drug responsive domains (DRDs), polypeptides that can regulate the abundance and/or activity of the IL15 upon binding of the DRD with a ligand. Also provided herein are components for making the modified TILs and methods for making and using the modified TILs.

Abstract: The present disclosure is directed to an engineered protein (e.g., a chimeric protein) comprising one or more of an extracellular domain, a transmembrane domain and/or an intracellular domain, which are capable of binding a negative signal and functioning as a sink, dominant negative, or signal inverter for the negative signal. The disclosure is further directed to methods of generating a modified cell expressing one or more of the engineered proteins (e.g., chimeric proteins), and methods of using the modified cells in treating a disease or a condition in a subject in need thereof.