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

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 possible clinical use in patients with Hodgkin's lymphoma, we have chosen murine anti-CD30 hybridoma Ki-4 generate high-affinity single-chain variable fragment (scFv). Hybridoma V-genes were polymerase chain reaction-amplified, assembled, cloned expressed mini-library display filamentous phage. Functional scFv obtained by selection binding phage lymphoma-derived, CD30-expressing cell line L540Cy. selected was specifically bind overlapping epitope antigen kinetics similar those original antibody. subsequently fused deletion mutant Pseudomonas exotoxin A (ETA). resulting Ki-4(scFv)-ETA binds CD30+ L540Cy inhibits protein synthesis 50% at concentration (IC50) 43 pM. This promising candidate further evaluation lymphoma or other malignancies. © 1999 Cancer Research Campaign