Studies will be undertaken to gain further insight into the biological and biochemical effects of the human interferons so as to further elucidate their mechanism(s) of action and ascertain how they can best be employed therapeutically. One of the proposed aims is to produce polyclonal and monoclonal antibodies directed against the proteins induced in interferon-treated cells. These antibodies will be used to examine the interferon-treated cells, to ascertain whether the induced proteins synthesized in response to the different human interferons are structurally and antigenically related and to determine whether these interferon-induced proteins play a role in the action of the interferon-induced enzyme activities. Methodologies will also be developed and employed which will allow for a determination of the responsiveness of freshly removed tumor tissues to the effects of the different human interferons. This methodology will use as a measure of responsiveness to the interferons the ability of the tumor cells to synthesize the interferon-induced proteins. This measurement will be accomplished by using the antibodies directed against the interferon-induced proteins to either immunoprecipitate radioactively-labeled interferon-induced proteins from the interferon-treated tumor cells or to stain the interferon-treated tumor cells for the presence of the interferon-induced proteins. A determination of the rsponsiveness to the interferons could be made rapidly (in 24 hr) and would allow clinicians to select patients for interferon therapy that are capable of responding to the interferon. The interferons have been found to differ in their abilities to inhibit the replication of different viruses. This comparison will be extended to include other clinically relevant viruses (e.g., adenovirus and herpes simplex virus) to determine which of the interferons is best capable of inhibiting the replication of these viruses. Purified E. coli-derived Gamma interferon has been shown in this laboratory to have a lower specific activity than leukocyte-derived Gamma interferon. Studies will be undertaken to compare the structural and biological properties of leukocyte and E. coli-derived Gamma interferons and to determine whether this observed difference in specific activity is due to the absence of carbohydrate on the E. coli-derived Gamma interferon.
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