ELIMINATION OF ANTIGEN REACTIVE B CELLS

MEDAREX HAS EXCLUSIVE LICENSE TO SEVERAL MONOCLONAL ANTIBODIES (MABS) REACTIVE TO THE HIGH AFFINITY FC RECEPTOR FOR IGG (FCGRI), ON HUMAN MONOCYTES. THIS RECEPTOR IS A CRITICAL TRIGGER MOLECULE FOR ADCC BY THESE CELLS AND HAS BEEN SHOWN TO MEDIATE KILLING OF RED CELL TARGETS AND TUMOR LIKE CELLS. WE PROPOSE TO DETERMINE THE FEASIBILITY OF USING THESE REAGENTS TO ELIMINATE ANTIGEN REACTIVE B CELLS. STUDIES BY CONSULTANTS TO MEDAREX INDICATE THAT THIS APPROACH PERMITS LYSIS OF B CELL-LIKE TARGETS (HYBRIDOMA CELLS EXPRESSING SURFACE IG). WE NOW PROPOSE TO DEMONSTRATETHAT NORMAL B CELLS REACTIVE TO PARTICULAR ANTIGENS CAN BE KILLED IN A SIMILAR FASHION. OUR SPECIFIC AIMS ARE, THEREFORE, TO INVESTIGATE, USING AN IN VITRO MOUSE MODEL SYSTEM, WHETHER OUR ANTI-FCGRI MABS, WHEN COUPLED TO ANTIGEN (TNP) CAN 1) MEDIATE KILLING OF RESTING ANTIGEN REACTIVE B CELLS BY HUMAN MONOCYTES; 2) TARGET HUMAN MONOCYTES TO ELIMINATE ANTIGEN REACTIVE B CELLS; AND 3) MEDIATE ELIMINATION OF PLAQUE FORMING CELLS.