PRODUCTION OF COMPOSITE MONOCLONAL IMMUNOGLOBULINS

MURINE MONOCLONAL ANTIBODIES ARE NOT USEFUL FOR REPEATED ADMINISTRATION TO MAN BECAUSE OF THE NUMBER OF FOREIGN ANTIGEN DETERMINANTS THEY CONTAIN. PRODUCTION OF HUMAN MONOCLONAL ANTIBODIES WOULD BE DESIR-ABLE FOR A VARIETY OF APPROACHES IN PROPHYLAXIS AND THERAPY OF DISEASE, AND ALSO IN PROTECTION AGAINST CONTACT WITH NOXIOUS AGENTS. WE PROPOSE DEVELOPMENT OF A PROCEDURE THAT WILL PERMIT RAPID ISOLATION OF COMPOSITE HUMAN MONOCLONAL ANTIBODIES IN WHICH PRE-SELECTED MOUSE VARIABLE REGIONS HAVE BEEN SUBSTITUTED FOR THE HUMAN VARIABLE REGIONS CONVEYING ANY DESIRED SPECIFICITY TO THE HUMAN ANTIBODY. THE PROCEDURES PROPOSED INVOLVE A MUNIMUM OF IN VITRO DNA RECONSTRUCTION WORK OR CLONE SCREENING AND THEREFORE WOULD BE APPLICABLE FOR PRODUCTION OF A WIDE VARIETY OF ANTIBODIES. POTENTIAL APPLICATIONS INCLUDE PRE-TREATMENT OF INDIVIDUALS EXPOSED TO INFECTIOUS OR TOXIC AGENTS AND RAPID PROTECTION AGAINST SPREAD OF INFECTIONS.