Following the invention in 1975 of in-vitro production of monoclonal antibodies using mouse myeloma cells, there has been widespread interest in the production of human monoclonal antibodies, mainly because mouse antibodies cannot be used for immunotherapy as they provoke an immune reaction.
However, at that time there were no suitable human myeloma cells available and the problems incurred in attempts to generate such cells have meant that the potential benefits of monoclonal antibody therapy have not been fully realised. Numerous researchers have tried to immortalise antibody-producing human B-cells with the Epstein-Barr virus (EBV), but EBV does not preferentially immortalise lymphoblasts engaged in antibody responses. In addition, EBV-infected cell lines produce very low levels of antibodies and tend to be unstable with respect to antibody production.
Enormous resources have been ploughed into complex and costly alternative methods, but although these have enjoyed some success, they are expensive, time-consuming and are unlikely to create the ideal antibodies that are produced by the human body. Only a successful fusion between human myeloma cells and antibody producing B-cells can lead to in- vitro production of unlimited quantities of important and beneficial antibodies that the body's immune system produces.
The research team at the University of Cambridge has succeeded in making a generation of stable human hybridomas capable of producing genuine human monoclonal antibodies. These cell lines have been successfully fused with antibody-producing human B-cells to generate a large number of hybridomas. For example, fusions with ouabain- sensitive Epstein-Barr virus-transformed cells as well as with fresh tonsil and blood lymphocytes have generated numerous stable hydridomas that do not lose immunoglobulin secretion over many months of continuous growth. Molecular studies of 30 hybridomas produced by fusions to tonsil and blood lymphocytes have confirmed that these antibodies are representative of antibodies from populations of human lymphocytes. It is thus anticipated that they will prove more useful in the study of human antibody responses than antibodies produced by other methods.
Innovative Aspects: The human myeloma cell line contains unique genetic markers, and the hybridomas it forms produce very high levels of antibodies with stable continuous long-term secretion.
Main Advantages: Given time it should be possible to immortalise most of the antibodies that the human body produces in reaction to infections, cancer and other pathological conditions. It can be envisaged that the use of this exciting new cell line will become the preferred method for immortalising human antibodies in a wide spectrum of pathological conditions. This will produce a range of antibodies potentially more useful for the generation of therapeutic treatments for infectious diseases, and possibly also for a range of autoimmune conditions. If monoclonal antibodies could be raised against tumours, it might enable the discovery of tumour-specific antigens that in turn could be used as anti-cancer vaccines. Furthermore, since it is possible to create hybridomas even with non-lymphoid cells, fusions with cells that secrete other beneficial proteins are likely to lead to hybridoma factories for other useful human proteins.
Source: http://pharmalicensing.com/licensing/displicopp/3384