Compositions and methods for adoptive cell therapy

An engineered immune cell comprising:

• (a) a first prodrug converting enzyme and/or a nucleic acid encoding the prodrug converting enzyme, wherein the first prodrug converting enzyme is expressed in the cytoplasm of the immune cell, optionally wherein the first prodrug converting enzyme is selected from among a carboxypeptidase, a β-lactamase, a glucosidase, a nitroreductase, and carboxypeptidase A;
• and
• (b) a receptor that binds to a target antigen and/or nucleic acid encoding the receptor, wherein the receptor targets the engineered immune cell to a site of inflammation, pathogenic infection or a target tissue or organ, and
• (c) a second prodrug converting enzyme and/or a nucleic acid encoding the second prodrug converting enzyme, wherein the second prodrug converting enzyme is:
• expressed on the surface of the immune cell;
• attached to the surface of the cell by a GPI anchor;
• fused to a transmembrane domain, optionally wherein the transmembrane domain is a CD8 transmembrane domain:
• or
• is secreted, and
• optionally wherein the target tissue is bone marrow.