An anti-CD30 single-chain Fv selected by phage display and fused to Pseudomonas exotoxin A (Ki-4(scFV)-ETA') is a potent immunotoxin against a Hodgkin-derived cell line

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作者：

A Klimka，S Barth，B Matthey，RC Roovers，H Lemke，H Hansen，JW Arends，V Diehl，HR Hoogenboom，A Engert

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摘要：

The human CD30 receptor is highly overexpressed on the surface of Hodgkin Reed-Sternberg cells and has been shown to be an excellent target for selective immunotherapy using monoclonal antibody-based agents such as immunotoxins. To construct a new recombinant immunotoxin for possible clinical use in patients with Hodgkin's lymphoma, we have chosen the murine anti-CD30 hybridoma Ki-4 to generate a high-affinity Ki-4 single-chain variable fragment (scFv). Hybridoma V-genes were polymerase chain reaction-amplified, assembled, cloned and expressed as a mini-library for display on filamentous phage. Functional Ki-4 scFv were obtained by selection of binding phage on the Hodgkin lymphoma-derived, CD30-expressing cell line L540Cy. The selected recombinant Ki-4 scFv was shown to specifically bind to an overlapping epitope on the CD30 antigen with binding kinetics similar to those of the original antibody. The Ki-4 scFv was subsequently fused to a deletion mutant ofPseudomonasexotoxin A (ET). The resulting immunotoxin Ki-4(scFv)-ET specifically binds to CD30+L540Cy cells and inhibits the protein synthesis by 50% at a concentration (IC50) of 43 pM. This recombinant immunotoxin is a promising candidate for further clinical evaluation in patients with Hodgkin's lymphoma or other CD30+malignancies. 1999 Cancer Research Campaign

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关键词：

CD30 Ki-4 phage display recombinant immunotoxin Hodgkin's lymphoma

DOI：

10.1038/sj.bjc.6690488

被引量：

251

年份：

1999