TUMOR NECROSIS FACTOR (TNF) IS A 17,000-DALTON POLYPEPTIDE SECRETED BY MACROPHAGES WHICH HAS ANTITUMOR CYTOLYTIC ACTIVITY.

TUMOR NECROSIS FACTOR (TNF) IS A 17,000-DALTON POLYPEPTIDE SECRETED BY MACROPHAGES WHICH HAS ANTITUMOR CYTOLYTIC ACTIVITY. TNF DOES NOT APPEAR TO AFFECT NORMAL CELLS AND HAS BEEN SHOWN REPEATEDLY TO EITHER KILL OR PREVENT THE GROWTH OF TUMOR CELLS IN BOTH IN VITRO AND IN VIVO MODEL SYSTEMS. TNF IS THOUGHT TO EXERT ITS EFFECT THROUGH A PROCESS INITIATED BY THE BINDING OF TNF TO SPECIFIC CELL SURFACE RECEPTORS. THE LONG-TERM OBJECTIVE OF THIS PROPOSAL IS TO PRODUCE MONOCLONAL ANTIBODIES SPECIFIC FOR THE TNF RECEPTOR. SUCH ANTIBODIES WILL THEN BE USED TO 1.PURIFY LARGE QUANTITIES OF RECEPTOR FOR USE IN IN VIVO ANTITUMOR IMMUNITY STUDIES, 2.PRODUCE HIGHLY TUMOR-SPECIFIC ANTIBODY-TOXIN/RADIOLABEL CONJUGATES FOR CANCER DIAGNOSIS AND THERAPY, AND PHASE I STUDIES WILL ATTEMPT TO IDENTIFY A SPECIFIC TNF RECEPTOR BY 1.CROSS-LINKING LABELED TNF TO CELL SURFACE RECEPTORS WITH SUBSEQUENT SOLUBILIZATION AND VISUALIZATION OF THE TNF-RECEPTOR COMPLEX, AND 2.TNF-AGAROSE AFFINITY CHROMATOGRAPHY OF SOLUBILIZED LABELED CELL MEMBRANE PROTEINS. UNEQUIVOCAL IDENTIFICATION OF THE TNF-RECEPTOR, AND THE DETERMINATION OF SOME OF ITS PHYSICAL AND CHEMICAL CHARACTERISTICS IS A NECESSARY STEP TOWARDS INITIATION OF PHASE II STUDIES.