Preferred Label : Autologous iC9-GD2CAR-CD28-CD3zeta-IL-15-expressing T-lymphocytes;
NCIt synonyms : Autologous iC9-GD2CAR-CD28-CD3zeta-IL-15-expressing T-cells; iC9.GD2.CAR.IL-15 T-cells;
NCIt definition : A preparation of autologous T-lymphocytes that have been transduced with the retroviral
vector SFG, a Moloney murine leukemia (Mo-MuLV) virus-based vector, expressing both
an extracellular domain consisting of interleukin 15 (IL-15) and a GD2-specific chimeric
antigen receptor (CAR) derived from the monoclonal antibody 14G2a, linked to the CD28
and CD3zeta (TCRzeta; CD247) costimulatory signaling domains and containing the suicide
gene, inducible caspase 9 (iCasp9 or iC9), with potential immunomodulating and antineoplastic
activities. Upon administration, the autologous iC9-GD2CAR-CD28-CD3zeta-IL-15-expressing
T-lymphocytes recognize, bind to and induce selective cytotoxicity in GD2-expressing
tumor cells. IL-15 is a pro-survival cytokine that promotes T-cell persistence and
potentiates the immune response against tumor cells. Incorporation of the costimulatory
signaling domains increases T-cell function, expansion, and survival. 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, which binds to the FKBP12-F36V drug-binding domain, activates caspase 9 and
results in apoptosis of the administered CAR T-cells, can be administered. GD2, a
disialoganglioside and tumor-associated antigen (TAA), is overexpressed on the surface
of neuroblastoma cells and other neuroectoderm-derived neoplasms and is minimally
expressed on normal, healthy cells.;
NCI Metathesaurus CUI : CL950701;
Origin ID : C158732;
UMLS CUI : C5203919;
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
