Autologous Anti-GD2-CAR-BBz-iCasp9 Retroviral Vector-transduced T Lymphocytes - CISMeF
Autologous Anti-GD2-CAR-BBz-iCasp9 Retroviral Vector-transduced T LymphocytesNCIt concept
Preferred Label : Autologous Anti-GD2-CAR-BBz-iCasp9 Retroviral Vector-transduced T Lymphocytes;
NCIt synonyms : Autologous Anti-GD2-CAR-BBz-transduced T Lymphocytes; Autologous GD2 CAR-BBz-iCasp9 T Cells; Autologous 14g2a-CD8.BB.z.iCasp9-expressing CAR T Cells;
NCIt definition : 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.;