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Anti-EGFRvIII immunotoxin MR1-1

A recombinant immunotoxin consisting of single-chain variable domain fragment antibody directed against the tumor-specific antigen EGFRvIII (MR1scFv) fused to domains II and III of the Pseudomonas exotoxin (PE38KDEL), with potential antineoplastic activity. Upon administration, the antibody moiety of anti-EGFRvIII immunotoxin MR1-1 binds to EGFRvIII; upon internalization, the exotoxin portion inhibits protein synthesis, resulting in a reduction in tumour cell proliferation of EGFRvIII- expressing tumour cells. EGFRvIII, a type III in-frame deletion mutation of the epidermal growth factor receptor (EGFR) gene, is expressed by a variety of cancers, including glioblastoma multiforme, non-small lung carcinoma, and breast carcinoma. Compared to intact IgG antibodies, single-chain antibodies such as MR1scFv are smaller and may penetrate tumours better. Pseudomonas exotoxin PE38KDEL was modified to remove the natural cell binding domain.

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