autologous anti-GD2-CAR-BBz-iCasp9 retroviral vector-transduced T lymphocytes

A preparation of genetically modified autologous T lymphocytes transduced with a retroviral vector encoding a chimeric antigen receptor (CAR) consisting of a single chain variable fragment (scFv) derived from the monoclonal antibody 14g2a that is specific for the disialoganglioside GD2 and the co-stimulatory domain 4-1BB (CD137) coupled to the zeta chain of the TCR/CD3 complex (CD3-zeta), and fused with the suicide gene inducible caspase 9 (iCasp9), with potential immunomodulating and antineoplastic activities. Upon intravenous administration of the autologous anti-GD2-CAR-BBz-iCasp9 retroviral vector-transduced T lymphocytes, these cells target the GD2 antigen on tumor cells, thereby providing selective toxicity towards GD2-expressing tumor cells. The tumor-associated antigen (TAA) GD2 is overexpressed on the surface of neuroblastoma cells and by other neuroectoderm-derived neoplasms, while it is minimally expressed on normal cells. iCasp9 consists of a human FK506 drug-binding domain with an F36V mutation (FKBP12-F36V) linked to human caspase 9. If the administered T cells lead to unacceptable side effects, the chemical homodimerizer AP1903 can be administered; this binds to the drug binding FKBP12-F36V domain and activates caspase 9, which results in the apoptosis of the administered T cells and enhances safety of this agent.