Compositions and methods for adoptive cell therapy for cancer

An engineered immune cell comprising:

• (a) a nucleic acid encoding a first prodrug converting enzyme, wherein the first prodrug converting enzyme is configured to be expressed in the cytoplasm of the immune cell and is selected from among a carboxypeptidase, a β-lactamase, a glucosidase, a nitroreductase, and carboxypeptidase A;
• (b) a chimeric antigen receptor comprising a first transmembrane domain, wherein the chimeric antigen receptor is expressed on the surface of the immune cell and binds to a tumor antigen on solid tumors, and/or a nucleic acid encoding the chimeric antigen receptor;
• and
• (c) a nucleic acid encoding a second prodrug converting enzyme, wherein the second prodrug converting enzyme
• (i) is configured to be secreted or
• (ii) is expressed on the surface of the immune cell and is
• (A) attached to the surface of the cell by a GPI anchor;
• or
• (B) fused to a second transmembrane domain;
• and
• wherein the first transmembrane domain of the chimeric antigen receptor is separate from the second transmembrane domain of the second prodrug converting enzyme, and
• wherein the engineered immune cell treats solid tumors that are resistant to CAR T cell therapy.