Small molecules for dual function positron emission tomography (PET) and cell suicide switches
The present invention includes an engineered cell comprising a chimeric antigen receptor (CAR) further comprising a nucleic acid molecule comprising a suicide gene comprising a ligand binding domain and a suicide domain wherein the ligand binding domain is capable of binding to radiolabeled tracer or a small molecule suicide switch. This invention also includes methods for inducing apoptosis of an engineered cell, methods for assessing the efficacy or toxicity of an adoptive cell therapy in a subject, methods for detecting the quantity of engineered T cells in a subject, methods for monitoring an immunotherapy treatment in a subject and methods of imaging engineered T cells in a subject. In some embodiments, the imaging is performed via Positron Emission Topography (PET). This invention further includes a chemical inducer of dimerization (CID), wherein the CID is a Bis-Trimethoprim (Bis-TMP).
1 . An engineered cell comprising a chimeric antigen receptor (CAR) and further comprising a nucleic acid molecule comprising a suicide gene encoding a fusion protein comprising an E. coli dihydrofolate reductase (eDHFR) ligand binding domain and a suicide domain comprising an inducible caspase 9 (iCasp9) domain, wherein the fusion protein further comprises a linker consisting of 15 or 18 amino acids in length.
2 . The engineered cell of claim 1 , wherein the cell is a T cell.