WE PROMISE TO DEVELOP METHODS FOR THE LARGE-SCALE PRODUCTION OF HUMAN COLONY STIMULATING FACTORS (CSF) FROM NORMAL HUMAN PERIPHERAL BLOOD LYMPHOCYTES.

WE PROMISE TO DEVELOP METHODS FOR THE LARGE-SCALE PRODUCTION OF HUMAN COLONY STIMULATING FACTORS (CSF) FROM NORMAL HUMAN PERIPHERAL BLOOD LYMPHOCYTES. THE FERMENTATION METHODS EMPLOYED WILL BE SIMILAR TO THOSE USED FOR THE PRODUCTION OF NATURAL INTERLEUKIN-2. WE ARE PRODUCING HUMAN IL-2 FOR CLINICAL EVALUATION BY THE BIOLOGICAL RESPONSE MODIFIERS PROGRAM (BRMP). PURIFIED CSFS WILL BE TESTED IN PRECLINICAL SCREENING AND EVENTUALLY USED FOR EFFICACY STUDIES FOR ACCELERATED RESTORATION OF SUPPRESSED BONE MARROW FUNCTION IN CHEMOTHERAPY. IN PHASE I, SUITABLE ASSAY METHODS UTILIZING NORMAL HUMAN BONE MARROW AND SOFT AGAR CULTURE TECHNIQUES WILL BE DEVELOPED. FERMENTATION CONDITIONS WILL BE OPTIMIZED TO PROMOTE PRODUCTION OF CSF. ATTEMPTS WILL BE MADE TO MAXIMIZE PRODUCTION OF G-M OR MULTI-CSF SINCE THESE FACTORS ARE OF HIGHEST CLINICAL INTEREST. IN PHASE II OF THE PROPOSAL, SUITABLE METHODS FOR PURIFICATION AND SEPARATION OF COLONY STIMULATING ACTIVITIES WILL BE DEVELOPED. THESE METHODS WILL ALLOW BIOCHEMICAL AND BIOLOGICAL CHARACTERIZATION OF CSF. PRODUCTION AND PURIFICATION PROCESSES WILL BE SCALED UP TO PRODUCE SUFFICIENT MATERIAL FOR IN VIVO TESTING. AVAILABILITY OF PURE PRODUCT AND ASSAY METHODS FOR DISTINGUISHING VARIOUS TYPES OF CSFS WILL ALLOW CLONING AND EXPRESSION IN A SUITABLE ORGANISM