Preferred Label : Autologous iC9-GD2-CAR-expressing VZV-specific T Lymphocytes;
NCIt synonyms : Autologous iC9-GD2-CAR-VZV-CTLs;
NCIt definition : Genetically modified, autologous varicella zoster virus (VZV)-specific T-lymphocytes
transduced with a retroviral vector encoding a chimeric antigen receptor (CAR) specific
for the disialoganglioside GD2, which contains the signaling domains for the co-stimulatory
molecules CD28 and CD134 (OX-40), and the suicide gene, inducible caspase 9 (iCasp9
or iC9), with potential immunomodulating and antineoplastic activities. Upon intravenous
administration, iC9-GD2-CD28-OX40-expressing T lymphocytes target the GD2 antigen
on tumor cells for selective toxicity against GD2-expressing tumor cells. iCasp9 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
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 T-cells. Expression of the iCasp9
gene in T cells for adoptive transfer increases safety and broadens the scope for
their clinical applications. The tumor associated antigen GD2 is overexpressed on
the surface of almost all tumors of neuroectodermal origin. OX40 and CD28, both T-cell
surface-associated co-stimulatory molecules, are required for full T-cell activation.
An additional VZV vaccine can be administered to increase T-cell activity.;
NCI Metathesaurus CUI : CL454278;
Origin ID : C111989;
UMLS CUI : C3831436;
Semantic type(s)
- Cell [UMLS semantic type]
- chemical_or_drug_affects_cell_type_or_tissue
- chemical_or_drug_has_mechanism_of_action
- chemical_or_drug_has_physiologic_effect
- concept_is_in_subset
- has_target
