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  • A preparation of autologous T lymphocytes that are transduced with a retroviral vector encoding a chimeric antigen receptor (CAR) specific for the CD19 antigen, the suicide gene, inducible human caspase 9 (iCasp9 or iC9), and a truncated low-affinity nerve growth factor receptor (deltaNGFR), with potential immunomodulating and antineoplastic activities. The iCasp9 construct consists of the entire coding sequence for the human FK506-drug binding protein (FKBP12) with an F36V mutation (FKBP12-F36V) that is linked to the gene encoding human caspase 9, which is deleted of its endogenous caspase activation and recruitment domains. Upon intravenous administration, autologous iCASP9-CD19-expressing T lymphocytes are selectively toxic to CD19-expressing tumor cells. If the administered T cells lead to unacceptable side effects, the chemical homodimerizer AP1903 can be administered, which binds to the FKBP12-F36V drug binding domain, activates caspase 9, and results in apoptosis of the administered CAR19 T cells. The CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. Prior to administration, deltaNGFR, is used to select the CAR19-transduced T cells for further enrichment by flow cytometry using an anti-NGFR antibody. Check for \'https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/C131214\' active clinical trials using this agent. (\'http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C131214\' NCI Thesaurus)
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