Antibodies are prepared by immunizing an animal so that its own immune system is triggered to produce antibodies against the antigens of interest. In the laboratory, mice and rats have been studied extensively. The animal is immunized at weekly intervals for 3 or 4 weeks with the antigen to be studied, and is finally sacrificed and its lymphocytes taken. In practice, this is done by removing the spleen of the animal, which is a rich source of lymphocytes, and preparing a fresh single-cell suspension from which lymphocytes can subsequently be isolated. Similarly the myeloma lines used are also of mouse and rat origin and established in tissue culture. An early observation was that inter-species hybridization is unreliable as resulting daughter cells tend to be unstable in their genetic constitution. Therefore mouse lymphocytes are fused with mouse myeloma lines and rat lymphocytes with rat myeloma lines.
In this book we are principally concerned with the application of the monoclonal antibody technology to medical practice. For this it would be desirable to have human monoclonal antibodies, i.e. MCA's prepared by the fusion of human B-lymphocytes with a human myeloma line. Until recently this has not proved possible. Firstly, it is clearly not always ethically possible to immunize human subjects with antigens of interest such as toxins, bacteria or malignant cells. Secondly, there have been great difficulties in producing stable, infection-free cell lines from human myelomas in culture. However, recent advances have made the production of stable human myeloma lines feasible whilst immunization problems have been overcome by obtaining for fusion lymphocytes from the lymph nodes of patients known to be suffering from particular disease, removed routinely and stable human hybrid cells obtained. When subsequent re-administration of these MCA's is contemplated for diagnostic or therapeutic purposes, human antibodies would have the overwhelming advantage that as a naturally occurring human protein they would not excite an immunological reaction in the recipient, which is always a concern when administering rat or mouse protein.
