autologous anti-CSPG4 CAR-iC9-expressing T lymphocytes

A preparation of T lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) specific for chondroitin sulfate proteoglycan 4 (CSPG4) and the suicide gene inducible caspase 9 (iCasp9 or iC9), with potential immunostimulating and antineoplastic activities. Upon administration, autologous anti-CSPG4 CAR-iC9-expressing T lymphocytes specifically target and bind to CSPG4-expressing tumor cells, resulting in tumor cell lysis. CSPG4 is overexpressed on a variety of tumor cell types. The iCasp9 safety switch consists of a full-length caspase 9, including its caspase recruitment domain, linked to a human FK506 drug-binding domain with an F36V mutation (FKBP12-F36V). If the administered CAR T cells lead to unacceptable side effects, the chemical homodimerizer AP1903 can be administered. AP1903 binds to the FKBP12-F36V drug-binding domain, activates caspase 9 and results in apoptosis of the administered CAR T cells.