Preferred Label : Autologous CD4 /CD8 EGFR806 Specific 4-1BB-CD3zeta-EGFRt-expressing CAR T Cells;
NCIt synonyms : Autologous EGFR806-specific CAR T Cells; Autologous CD4 /CD8 T Cells Expressing EGFR806-specific CAR/EGFRt; Autologous EGFR806 Specific CAR T Cells;
NCIt definition : A preparation of CD4 and CD8 autologous T-lymphocytes transduced with a lentiviral
vector expressing a chimeric antigen receptor (CAR) 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),
with potential immunostimulating and antineoplastic activities. Depatuxizumab specifically
targets abnormal conformational states of EGFR, including the EGFR deletion mutation
variant III (EGFRvIII), and activating mutations, with very low affinity for wild-type
EGFR. Upon intravenous administration, the autologous CD4 /CD8 EGFR806 specific 4-1BB-CD3zeta-EGFRt-expressing
CAR T-cells are directed to and induce selective toxicity in EGFRvIII-expressing tumor
cells. Devoid of both ligand binding domains and tyrosine kinase activity, the expressed
EGFRt both facilitates in vivo detection of the administered, transduced T-cells and
can promote elimination of these cells through an anti-EGFR antibody-dependent cellular
cytotoxicity (ADCC) response. 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.;
NCI Metathesaurus CUI : CL935992;
Origin ID : C156883;
UMLS CUI : C4745144;
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