Preferred Label : Immunotoxin D2C7-(scdsFv)-PE38KDEL;
NCIt synonyms : D2C7-(scdsFv)-PE38KDEL Immunotoxin; D2C7-(scdsFv)-PE38KDEL;
NCIt definition : A recombinant immunotoxin fusion protein consisting of single-chain variable-region
antibody fragments (scFvs), which contain disulfide stabilized heavy- (Vh) and light-
(Vl) chain variable regions of the monoclonal antibody D2C7 (D2C7-scdsFv), targeting
both the wild-type form (EGFRwt) and the in-frame deletion mutant form (EGFRvIII)
of epidermal growth factor receptor (EGFR), and fused, via a 15-amino acid peptide
linker to domains II and III of the Pseudomonas exotoxin A (PE38KDEL) (D2C7-(scdsFv)-PE38KDEL),
with potential antineoplastic activity. Upon intratumoral administration by convection-enhanced
delivery, the scFv moiety of immunotoxin anti-EGFR scFv monoclonal antibody fragment
immunotoxin D2C7-(scdsFv)-PE38KDEL targets and binds to a specific amino acid epitope
present in the extracellular domain of both the EGFRwt and EGFRvIII proteins. This
binding facilitates the internalization of the immunotoxin by tumor cells. Inside
the cells, the exotoxin portion of the fusion protein binds to translation elongation
factor 2 (EF-2), and deactivates EF-2 through ADP ribosylation. This results in the
inhibition of protein synthesis, the induction of apoptosis and a reduction in cell
proliferation of EGFRwt/EGFRvIII-expressing tumor cells. Compared to intact IgG antibodies
and single-chain antibodies, scFvs are smaller with increased tumor-penetrating capacity
which may enhance therapeutic efficacy. The EGFR gene, a transmembrane receptor tyrosine
kinase, and its mutant form, EGFRvIII, which contains a deletion of exons 2-7 of the
EGFR gene, are frequently amplified and overexpressed in a variety of cancers. KDEL
increases the toxin's intracellular retention, thereby enhancing its cytotoxicity.;
Molecule name : D2C7-IT;
Origin ID : C119739;
UMLS CUI : C3898779;
Currated CISMeF NLP mapping
- Semantic type(s)
- UMLS correspondences (same concept)
- concept_is_in_subset
- has_target
