Preferred Label : Autologous CD4 /CD8 4-1BB-CD3zeta-EGFR806-CAR-EGFRt/4-1BB-CD3zeta-CD19-CAR-HER2tG-expressing
CARs T Cells;
NCIt synonyms : Autologous CD4 /CD8 T Cells Expressing EGFR806-specific CAR/EGFRt and CD19-specific
CAR/HER2tG; Autologous EGFR806-specific CAR T Cells; Autologous EGFR806xCD19 Bispecific CAR T Cells;
NCIt related terms : Autologous CD4 /CD8 4-1BB-CD3zeta-EGFR806-CAR-EGFRt/4-1BB-CD3zeta- CD19-CAR-HER2tG-expressing
CARs T Cells;
NCIt definition : A preparation of CD4 and CD8 autologous T-lymphocytes transduced with a lentiviral
vector that co-expresses two different second generation chimeric antigen receptors
(CARs), one composed of a short chain variable fragment (scFv) binding domain derived
from depatuxizumab, a human anti-epidermal growth factor receptor (EGFR) monoclonal
antibody (MAb806; ABT-806), coupled to the zeta chain of the TCR/CD3 complex (CD3-zeta)
and the signaling domain of 4-1BB (CD137), and linked to a truncated form of the human
epidermal growth factor receptor (EGFRt), and one composed of a short chain variable
fragment (scFv) binding domain derived from an anti-CD19 monoclonal antibody, coupled
to CD3-zeta) and 4-1BB, and linked to a truncated form of the human epidermal growth
factor receptor 2 (HER2tG), with potential immunostimulating and antineoplastic activities.
Upon intravenous administration, the autologous CD4 /CD8 4-1BB-CD3zeta-EGFR806-CAR-EGFRt/4-1BB-CD3zeta-
CD19-CAR-HER2tG-expressing CARs T-cells are directed to, bind to, and induce selective
toxicity in EGFR deletion mutation variant III (EGFRvIII)-expressing tumor cells.
The binding of these T-cells to CD19 expressed on B-cells enhances their expansion
and prolongs their persistence in vivo, thereby increasing the efficacy of these CAR
T-cells. Devoid of both ligand binding domains and tyrosine kinase activity, the expressed
EGFRt and HER2tG facilitate in vivo detection of the administered, transduced T-cells
and can promote elimination of these cells through an antibody-dependent cellular
cytotoxicity (ADCC) response. HER2tG allows for enhanced binding by trastuzumab. EGFRvIII,
an in-frame deletion of exons 2-7 in the EGFR gene, is overexpressed by a variety
of cancer cell types but absent in normal, healthy cells. It plays a key role in tumor
cell proliferation, tumor angiogenesis and resistance to both radio- and chemotherapy.
Depatuxizumab specifically targets abnormal conformational states of EGFR, including
EGFRvIII, and activating mutations, with lower affinity for wild-type EGFR. CD19,
a transmembrane phosphoglycoprotein is expressed on the surface of cells in the B-lineage.;
NCI Metathesaurus CUI : CL936781;
Origin ID : C157090;
UMLS CUI : C4761464;
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
