Cellular and molecular approaches to developing human monoclonal antibodies as drugs

Attempts to bring murine monoclonal antibodies into clinical therapeutic use have always been thwarted by the body's reaction to foreign antigens. Although there has been some success with the use of murine monoclonal antibodies in the control of renal transplant rejection, its potential will remain limited. The solution then is to produce human mAbs, which are much less immunogenic in the patient and therefore, allow repeated administration. However, for the past decade, efforts to produce human monoclonal antibodies were focused on using the hybridoma fusion technique and Epstein-Barr virus transformation to generate lymphoblastoid cell lines. It is now certain that these two methods in their present form will yield neither the variety nor the quantity of human monoclonal antibodies sufficient for therapeutic use. A compromise approach which is to "humanise" murine antibodies by substituting up to 90-95% of their amino acids with human sequences will most likely become the method of choice in human monoclonal antibody production. These "chimeric" monoclonal antibodies have been shown to be much less immunogenic in patients and is a sign that monoclonal antibodies will soon be an important mode of immunotherapy.