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Human monoclonals produced.

Human monoclonals produced

Researchers from the National Institutes of Health (NIH) report they have coaxed monoclonal antibodies from a human cell line. The feat may remove a limitation of conventional monoclonal antibodies imposed on them by their heritage.

Monoclonal antibodies are widely used in medical diagnosis and are hot prospects as therapeutic agents. They are currently produced by fusing antibody-producing spleen cells from rodents and "immortal" rodent cancer cells.

But the antibodies, in as much as they come from rodent cells, are foreign to humans. Many researchers believe that people will build up an immune response after repeated injections of the antibodies, and various approaches to getting human cells to produce monoclonals have been tried.

Producing human monoclonals the same way rodent monoclonals are produced is out -- few people would be willing to give up their spleens. White cells in the bloostream also produce antibodies, but hybrids of human white blood cells and cancer cells tend to lose crucial chromosomes.

Another approach is to vaccinate a person with a protein, collect antibody-producing white blood cells, "immortalize" those cells with Epstein-Barr virus and select the cells producing the desired antibodies. While this technique has generated monoclonals, there is a limiting factor: The antibody in question has to be against a fairly benign substance so that a person could be vaccinated with it.

The NIH group figured out a way to circumvent the vaccination step, which they describe in the Oct. 24 SCIENCE. They started with a general population of white blood cells donated by healthy individuals, and exposed the cells to fluorescently tagged proteins. The proteins stuck to cells producing antibodies against them, and a cell sorter picked out the protein/white blood cell complexes. The white cells were then immortalized with Epstein-Barr virus.

Abner Louis Notkins of the National Institute of Dental Research, one of the investigators, says the advantage of the procedure is that the antibody-producing cells can be obtained without vaccinating the patient. Larry Steinman of Stanford University, who is working on a way to put human and mouse antibody genes into bacteria so that the bacteria produce a "hybrid" antibody, says the all-human approach could prove better than the hybrid approach if it works for other proteins besides the two tested. "If you can get human monoclonal antibody production totally in vitro," he says, "it's really a major advance."
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Title Annotation:monoclonial antibodies
Publication:Science News
Date:Nov 1, 1986
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