IFN-GAMMA BIOASSAYS

IFN- IS CURRENTLY BEING TESTED FOR THE TREATMENT OF A WIDE RANGE OF DISEASES INCLUDING AUTOIMMUNE AND INFECTIOUS DISEASES, SOLID TUMORS AND HEMATOLOGIC MALIGNANCIES. AS WITH OTHER BIOLOGICAL RESPONSE MODIFIERS, IT IS DIFFICULT TO PREDICT THE OPTIMAL DOSE FOR THE DESIRED IN VIVO EFFECT, AND TWO INDIVIDUALS MAY RESPOND VERY DIFFERENTLY TO THE SAME DOSE. IT IS NOW POTENTIALLY POSSIBLE TO MONITOR THE IN VIVO BIOACTIVITY OF IFN- SINCE THIS LYMPHOKINE, AND NO OTHERS TO DATE, DRAMATICALLY INCREASES THE NUMBER OF TYPE I FC RECEPTORS FOR IGG (FC RI) ON HUMAN MONOCYTES AND POLYMORPHONUCLEAR NEUTROPHILS (PMNS). MEDAREX HAS EXCLUSIVE RIGHTS TO MONOCLONAL ANTIBODIES (MABS) WHICH ARE UNIQUELY SUITED TO THE MEASUREMENT OF FC RI. RESEARCH OUTLINED IN THIS PROPOSAL IS DESIGNED TO DEVELOP AND TEST AN ELISA ASSAY FOR QUANTITATIVEANALYSIS OF BIOACTIVE IFN- , AND TO DEVELOP AND TEST MAB-BASED REAGENTS TO EVALUATE THE MAGNITUDE OF A GIVEN PATIENT'S RESPONSE TO IFN- IN VIVO. WE ANTICIPATE THAT THESE ASSAYS WILL SERVE AS PROTOTYPES FOR THE IN VIVO AND IN VITRO ANALYSIS OF RESPONSE TO OTHER IMMUNE CYTOKINES.