Fifty years ago, researchers developed the first method for mass production of monoclonal antibodies (mAbs), known as hybridoma technology. This invention revolutionized biomedical research and enabled the development of numerous therapies, diagnostic tests, and laboratory tools that are still in use today. However, this approach has limitations, as fusion yields between short-lived antibody-producing cells and immortal myeloma cells are low.
To improve these yields and increase the production of new antibodies, the authors addressed two main limitations : the random mixing of myeloma cells with spleen cells from immunized mice, and the low efficiency of the conventional fusion process (polyethylene glycol). Using flow cytometry with a panel of five surface markers, combined with antibody secretion assays, they identified the antibody-secreting cells (ASCs) most likely to pair successfully. They then developed a strategy combining cell sorting with targeted electrofusion of the most promising ASCs, which enabled them to obtain viable hybridomas in 100% of cases, compared with only 40% for electrofusion of unsorted cells.
The optimization of hybridoma technology described in this work paves the way for a high-yield method of producing monoclonal antibodies by cell fusion. It could facilitate broader use of this fundamental technique and reduce reliance on animals in certain contexts, since higher fusion yields would require fewer animals to be immunized.
Contact : Anne Wijkhuisen (anne.wijkhuisen@cea.fr)
Hybridoma technology is a method for mass-producing antibodies in a hybrid cell line generated by fusing antibody-producing B lymphocytes with an immortalized myeloma cell line, now referred to as a hybridoma cell.