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Generation of a humanised single chain Fv (Scfv) derived from the monoclonal Eric-1 recognising the human neural cell
H A Whittington1, J Hancock, J T Kemshead
1Division of Oncology, University of Bristol, United Kingdom.
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 adrenal medulla. Anti-NCAM antibodies have been used for the treatment and diagnosis of a number of tumours, including neuroblastoma. However, whole antibody exhibits poor penetration into solid tumour deposits and rapid systemic clearance upon repeated administration due to development of a human antimouse antibody (HAMA) response.
Procedure:
To overcome these problems, recombinant DNA techniques have been used to humanise and assemble the ERIC-1 immunoglobulin variable heavy (VH) and light (VL) chains into a single chain Fv (scFv).
Results:
Three humanised scFv clones were identified which differ from the predicted humanised sequence by occasional amino acid changes, but these maintain the same specificity as the original ERIC-1 MoAb.
Conclusions:
The humanised scFv may prove to be a useful reagents in the treatment and diagnosis of a variety of neuroectodermal tumours and can clearly form a suitable template for the generation of a fully humanised ERIC-1 MoAb.