Affiliations: [a] University of East London, England | [b] Tenovus Research Laboratory, Southampton, England | [c] ICRF Cancer Medicine Research Unit, St. James University Hospital, Leeds, England | [d] Guys Medical School, London, England | [e] Dept. Dermatology, Royal London Hospital, London, England
Correspondence:
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Corresponding author: Dr. M.B. Spellerberg, Tenovus Research Laboratory, Southampton University Hospital, Southampton, SO16 6YD, U.K.
Abstract: A heterohybridoma cell line producing the human monoclonal antibody (MoAb) MDT.1 has been established. The heavy chain of MoAb MDT.1 is encoded by the VH gene segment V4-34 (previously designated VH4-21), and the light chain is encoded by the Vκ1-L12a gene segment, both in germline configuration. MDT.1 has reactivity against lipid A, double- and single-stranded DNA, red blood cell associated i antigen, and ganglioside antigens. In a panel of tumour cell lines, MDT.1 reacted specifically with melanoma cells and other tumour cells of neuroectodermal origin. Cellular recognition appears to be via tumour-associated ganglioside antigens, and may involve the minimal essential epitope NeuNacα2→3Galβ1→-4Glc-. Binding to ganglioside antigen is inhibited by the monoclonal anti-idiotypic antibody 9G4. Since the 9G4 idiotope is located in framework region 1 (FWR1) of V4-34-encoded antibodies, this region is likely to be involved, either directly or indirectly, in ganglioside binding. The complementarity-determining region 3 (CDR3) of MDT.1 is arginine rich, with five out of 12 residues being arginine and these residues are candidates for interaction with the negatively charged ganglioside. The ability of MoAb MDT.1 to recognise ganglioside antigens is associated with potentially useful anti-tumour activity.
Keywords: human monoclonal antibody, melanoma, ganglioside, autoantibody
