A novel recombinant immunotoxin-based therapy targeting wild-type and mutant EGFR improves survival in murine models of glioblastoma
نویسندگان
چکیده
Both the amplification of the gene coding for wild-type (wt) epidermal growth factor receptor (EGFR) and the overexpression of the EGFR deletion mutant, commonly known as EGFRvIII, are hallmarks of glioblastoma. We have recently reported a novel, recombinant immunotoxin, D2C7-(scdsFv)-PE38KDEL, that targets both wt EGFR and EGFRvIII, exhibiting potent antineoplastic effects against established murine gliomas.
منابع مشابه
Antitumor efficacy of D2C7-(scdsFv)-PE38KDEL, a novel immunotoxin targeting EGFRwt and EGFRvIII, by convection-enhanced delivery in orthotopic brain tumor mouse models
Objective The epidermal growth factor receptor (EGFR) gene is most frequently amplified and overexpressed, along with its truncated mutant, EGFRvIII, in glioblastomas. We tested the antitumor efficacy of the recombinant immunotoxin, D2C7-(scdsFv)-PE38KDEL (D2C7-IT), which is reactive with a 55-amino acid (AA) region present in the extracellular domain of both EGFRwt and EGFRvIII proteins (Figur...
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Background: Epidermal growth factor receptor (EGFR) plays an important role in the progression and tumorigenesis of the various cancers. In this regards, anti-EGFR antibodies are valuable approved therapeutics for the EGFR over-expressing cancers. However, the occurrence of mutations in the EGFR and/or KRAS genes; a common phenomenon which is seen in many cancers, lead to the r...
متن کاملConstruction of an immunotoxin, D2C7-(scdsFv)-PE38KDEL, targeting EGFRwt and EGFRvIII for brain tumor therapy.
PURPOSE The EGF receptor gene (EGFR) is most frequently amplified and overexpressed, along with its deletion mutant, EGFRvIII, in glioblastoma. We tested the preclinical efficacy of the recombinant immunotoxin, D2C7-(scdsFv)-PE38KDEL, which is reactive with a 55-amino acid (AA) region present in the extracellular domain of both EGFRwt (583-637 AAs) and EGFRvIII (292-346 AAs) proteins. EXPERIM...
متن کاملAssessment of epidermal growth factor receptor status in glioblastomas
Objective(s): Our previous study showed that a newly designed tracer radioiodinated 6-(3-morpholinopropoxy)-7-ethoxy-4-(3'-iodophenoxy)quinazoline ([125I]PYK) is promising for the evaluation of the epidermal growth factor receptor (EGFR) status and prediction of gefitinib treatment of non-small cell lung cancer. EGFR is over-expressed and mutated also in glioblastoma. In the present study, the ...
متن کاملEGFR/EGFRvIII-targeted immunotoxin therapy for the treatment of glioblastomas via convection-enhanced delivery
Glioblastoma is the most aggressive malignant brain tumor among all primary brain and central nervous system tumors. The median survival time for glioblastoma patients given the current standard of care treatment (surgery, radiation, and chemotherapy) is less than 15 months. Thus, there is an urgent need to develop more efficient therapeutics to improve the poor survival rates of patients with ...
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