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- NCIT_C119739 IAO_0000115 "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." @default.
- NCIT_C119739 NCIT_A7 NCIT_C101140 @default.
- NCIT_C119739 NCIT_A7 NCIT_C17068 @default.
- NCIT_C119739 NCIT_NHC0 "C119739" @default.
- NCIT_C119739 NCIT_P106 "Pharmacologic Substance" @default.
- NCIT_C119739 NCIT_P107 "Immunotoxin D2C7-(scdsFv)-PE38KDEL" @default.
- NCIT_C119739 NCIT_P108 "Immunotoxin D2C7-(scdsFv)-PE38KDEL" @default.
- NCIT_C119739 NCIT_P207 "C3898779" @default.
- NCIT_C119739 NCIT_P322 "CTRP" @default.
- NCIT_C119739 NCIT_P329 "767013" @default.
- NCIT_C119739 NCIT_P330 "767013" @default.
- NCIT_C119739 NCIT_P399 "767013" @default.
- NCIT_C119739 normalizedInformationContent "100" @default.
- NCIT_C119739 referenceCount "1" @default.
- NCIT_C119739 hasExactSynonym "D2C7-(scdsFv)-PE38KDEL Immunotoxin" @default.
- NCIT_C119739 hasExactSynonym "D2C7-(scdsFv)-PE38KDEL" @default.
- NCIT_C119739 hasExactSynonym "D2C7-IT" @default.
- NCIT_C119739 hasExactSynonym "Immunotoxin D2C7-(scdsFv)-PE38KDEL" @default.
- NCIT_C119739 inSubset NCIT_C116977 @default.
- NCIT_C119739 inSubset NCIT_C116978 @default.
- NCIT_C119739 inSubset NCIT_C128784 @default.
- NCIT_C119739 inSubset NCIT_C176424 @default.
- NCIT_C119739 type Class @default.
- NCIT_C119739 isDefinedBy ncit.owl @default.
- NCIT_C119739 label "Immunotoxin D2C7-(scdsFv)-PE38KDEL" @default.
- NCIT_C119739 subClassOf NCIT_C119739 @default.
- NCIT_C119739 subClassOf NCIT_C1512 @default.
- NCIT_C119739 subClassOf NCIT_C1908 @default.
- NCIT_C119739 subClassOf NCIT_C1909 @default.
- NCIT_C119739 subClassOf NCIT_C307 @default.
- NCIT_C119739 subClassOf NCIT_C308 @default.
- NCIT_C119739 subClassOf NCIT_C575 @default.