CLONING OF HUMAN IMMUNOGLOBULINS FROM SCID-HU MICE

WE WILL DEVELOP A GENERAL TECHNIQUE TO IDENTIFY HUMAN MONOCLONAL ANTIBODIES (MABS). MURINE MABS ARE BEING USING IN MANY CLINICAL APPLICATIONS SUCH AS CANCER, SEPTIC SHOCK, AND TRANSPLANTATION. THE USE OF HUMAN MABS WOULD OBVIATE THE HUMAN ANTI-MOUSE MAB RESPONSE WHICH OFTEN BLUNTS THE CLINICAL USEFULNESS OF MAB IMMUNOTHERAPY. HOWEVER, FOR MOST INDICATIONS HUMAN MABS ARE VERY DIFFICULT OR IMPOSSIBLE TO OBTAIN AGAINST HUMAN ANTIGENS. THE USE OF HYPERIMMUNIZED SCID-HU MICE AS A SOURCE OF HUMAN B-CELLS, IN COMBINATION WITH BACTERIOPHAGE LAMBDA IMMUNOEXPRESSION CLONING TECHNIQUES, SHOULD YIELD HUMAN MABS AGAINST SELECTED HUMAN ANTIGENS. HUMAN MABS MADE BY THIS METHOD WOULD NOT HAVE THE SAME ANTIGENIC RESTRUCTIONS AS PREVIOUS METHODS AND THUS COULD BE OF GREAT PRACTICAL UTILITY.