A HUMAN T-CELL LYMPHOKINE CAPABLE OF INTERRUPTING THE PROLIFERATION OF MYELOID LEUKEMIA CELLS AND INDUCING TERMINAL DIFFERENTIATION TO MONOCYTE-MACROPHAGE HAS BEEN DESCRIBED.

A HUMAN T-CELL LYMPHOKINE CAPABLE OF INTERRUPTING THE PROLIFERATION OF MYELOID LEUKEMIA CELLS AND INDUCING TERMINAL DIFFERENTIATION TO MONOCYTE-MACROPHAGE HAS BEEN DESCRIBED. THIS ""MATURATION INDUCER'' (OR DIFFERENTIATION FACTOR) IS PRODUCED BY NORMAL T HELPER CELLS AND HAS BEEN SHOWN TO BE A T-CELL MEDIATOR OF MONOCYTIC CELL DEVELOPMENT. THIS ACTIVITY (M.W. 50,000) HAS RECENTLY BEEN PURIFIED BY BIOCHEMICAL PROCEDURES FROM CONDITIONED MEDIUM OF ACTIVATED NORMAL LYMPHOCYTES (INCLUDING OUR LAB) AND FROM A CONTINUOUS T-CELL LINE, HUT-102, AND SHOWN TO BE DISTINCT FROM THE COMMONLY KNOWN LYMPHOKINES INCLUDING INTERFERONS, COLONY STIMULATING FACTORS, MACROPHAGE ACTIVATING FACTOR, ETC. THIS APPLICATION IS AIMED AT THE PRODUCTION OF THIS LYMPHOKINE FOR ITS DEVELOPMENT AND EVALUATION AS AN IMMUNOAUGMENTIVE AGENT WITH POTENTIAL ANTILEUKEMIA ACTIVITY. RAT MONOCLONAL ANTIBODIES THAT HAVE ALREADY BEEN SHOWN TO BIND THE INDUCER ACTIVITY WILL BE EMPLOYED TO CONSTRUCT IMMUNOABSORBENT COLUMNS WHICH WILL BE USED WITH MEDIUM FROM HUT CELLS AND NORMAL LYMPHOCYTE CONDITIONED MEDIUM TO PURIFY THE INDUCER ACTIVITY. THE YIELD AND SPECIFIC ACTIVITY OF THE INDUCER THUS OBTAINED WILL BE DETERMINED ALONG WITH AN EVALUATION OF THE BIOLOGICAL ACTIVITY. THIS INCLUDES ANALYSIS OF HL-60 CELL DIFFERENTIATION TO MATURE MONOCYTIC CELLS AS JUDGED BY CELLULAR MORPHOLOGY, DIFFERENTIATION ANTIGENS, EXPRESSION OF MEMBRANE COMPLEMENT RECEPTORS, PHAGOCYTOSIS, ETC. SIMULTANEOUS ANALYSIS OF CELLULAR PROLIFERATION WILL BE INVESTIGATED BY CELL CYCLE PHASE KINETICS WITH FLOW CYTOMETRY. THE PURITY OF THE INDUCER OBTAINED WILL BE EVALUATED BY GEL ELECTROPHORESIS, COLUMN CHROMATOGRAPHY, AND HPLC. THESE TECHNICAL PROTOCOLS WILL FORM THE BASIS FOR SCALED UP PRODUCTION WHICH IS NECESSARY FOR FURTHER EVALUATION OF THE IMMUNE REGULATORY EFFECTS OF THIS LYMPHOKINE AS WELL AS ITS DEVELOPMENT AS A POTENTIAL ANTILEUKEMIA THERAPEUTIC.