Microenvironment actuated t-cells and uses thereof

An engineered T cell comprising

• a. a nucleic acid encoding a P-selectin-specific chimeric receptor polypeptide comprising
• i. an extracellular domain that specifically binds P-selectin;
• ii. a heterologous receptor polypeptide comprising one or more ligand-inducible proteolytic cleavage sites;
• and
• iii. an intracellular domain comprising a transcriptional activator, wherein binding of the extracellular domain to P-selectin induces cleavage of the heterologous receptor polypeptide at the one or more ligand-inducible proteolytic cleavage sites to release the intracellular domain, and
• b. a nucleic acid encoding a chimeric antigen receptor (CAR) polypeptide that is operably linked to a promoter that is responsive to the transcriptional activator of the released intracellular domain of the P-selectin-specific chimeric receptor polypeptide.