Preparation of an engineered safer immunotoxin against colon carcinoma based on the ribotoxin hirsutellin A

The FEBS Journal
Jaime Tomé-AmatJavier Lacadena

Abstract

Immunotoxins are chimeric proteins composed of an antibody domain that specifically directs the action of the toxic domain, resulting in the death of the targeted cells. Over recent years, immunotoxins have been widely studied and the number of different constructions has increased exponentially. Protein engineering has allowed the design of optimized versions of immunotoxins with an improved tumor binding affinity, stability or cytotoxic efficacy, although sometimes this has compromised the safety of the patient in terms of undesirable adverse secondary reactions. A triple mutant at three Trp residues (HtA3ΔW) of the ribotoxin hirsutellin A retains its specific ribonucleolytic activity, although cell internalization capacity is lacking. This toxin variant has been fused to the single chain variable fragment A33 (scFvA33). This immunoconjugate (IMTXA33HtA3ΔW) was produced in the methylotrophic yeast Pichia pastoris and purified using nickel-nitrilotriacetic acid affinity chromatography. Both target and toxic domains were characterized. The immunotoxin showed an exquisite specific binding against GPA33-positive culture cells, which results in the death of the targeted cells because of specific ribonucleolytic activity against ri...Continue Reading

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Dec 10, 2015·Disease Markers·A R RamaJ Prados
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Feb 24, 2017·Toxins·Miriam OlombradaLucía García-Ortega
Jul 5, 2019·Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms·Javier Oroz, Douglas V Laurents

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