Generation of a humanised single chain Fv (Scfv) derived from the monoclonal Eric-1 recognising the human neural cell adhesion molecule

Background, Murine monoclonal antibody (MoAb) ERIC-1 recognises an epitope on the neural cell adhesion molecule (NCAM) whose expression in paediatric and adult tissues is confined mainly to the brain, peripheral nerve, and ad renal medulla. Anti-NCAM antibodies have been used for the treatment and di agnosis of a number of tumours, including neuroblastoma. However, whole ant ibody exhibits poor penetration into solid tumour deposits and rapid system ic clearance upon repealed administration due to development of a human ant imouse antibody (HAMA) response. Procedure, To overcome these problems, rec ombinant DNA techniques have been used to humanise and assemble the ERIC-1 immunoglobulin variable heavy (V-H) and light (V-L) chains into a single ch ain Fv (scFv). Results. Three humanised scFv clones were identified which d iffer from the predicted humanised sequence by occasional amino acid change s, but these maintain the same specificity as the original ERIC-1 MoAb. Con clusions, The humanised scFv may prove to be a useful reagents in the treat ment and diagnosis of a variety of neuroectodermal tumours and can clearly form a suitable template for the generation of a fully humanised ERIC-1 MoA b. Med. Pediatr. Oncol. 36:243-246, 2001. (C) 2001 Wiley-Liss, Inc.