Preferred Label : Anti-GD2/PSMA/CD276 4SCAR-expressing T-cells;
NCIt synonyms : Anti-GD2/Anti-PSMA/Anti-CD276 4SCAR T Cells; Multi-4SCAR-T Cells; GD2/PSMA/CD276 4SCAR-T Cells;
NCIt definition : A preparation of T-cells that are genetically engineered to express fourth generation
chimeric antigen receptors (4SCARs) targeting the three tumor-associated antigens
(TAAs) prostate-specific membrane antigen (PSMA), disialoganglioside (GD2), and the
immune checkpoint molecule protein B7-homologue 3 (B7-H3, CD276), coupled to the costimulatory
signaling domains CD28, CD137, CD27 and the zeta chain of the T-cell receptor (CD3zeta;
CD3z), and fused with the suicide gene inducible caspase 9 (iCasp9), with potential
immunostimulating and antineoplastic activities. Upon administration, the anti-GD2/PSMA/CD276-4SCAR-expressing
T-cells are directed to and induce selective toxicity in GD2-, PSMA- and CD276-expressing
tumor 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. AP1903 binds
to the drug binding FKBP12-F36V domain and induces activation of caspase 9, which
results in the apoptosis of the administered T-cells and enhances safety of this agent.
PSMA, a type II transmembrane protein, is expressed on the membrane of prostatic epithelial
cells and overexpressed on prostate tumor cells as well as a variety of other solid
tumors, including brain tumor, neuroblastoma (NB) and some lymphoma tumor tissues.
CD276, a type I transmembrane protein and a member of the B7 co-stimulatory protein
superfamily, is highly expressed on many solid tumors including NB. It is a negative
regulator of the T-cell activation and plays a key role in tumor evasion. GD2 is overexpressed
on the surface of NB cells and by other neuroectoderm-derived neoplasms, while it
is minimally expressed on normal cells. CD28, CD137 and CD27, T-cell surface-associated
co-stimulatory molecules, are required for full T-cell activation and enhance both
proliferation of T-cells and antitumor activity.;
NCI Metathesaurus CUI : CL1661929;
Origin ID : C179257;
UMLS CUI : C5555558;
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
