INHIBITORS OF MACROPHAGES IN NEOPLASIA RELATIONSHIP

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During the next year we will begin studies to determine if monoclonal anti-p15E can be used to prevent or slow the growth of intraperitoneally or subcutaneously injected tumor cells or to prolong the survival of tumor-bearing animals. Three hybridoma cell lines producing monoclonal antibodies to different epitopes on retroviral p15E are currently being used to produce sufficiently large quantities of antibodies from the culture supernatants for these experiments. Mice will be treated with either intact IgG or the F(ab')2 fragments of the antibodies. Control mice will be injected with the same amounts of purified IgG of F(ab')2 fragments of the same isotype as the monoclonal anti-p15E used. The antibodies will be used singularly and in various combinations. Mice will be injected prior to and at regular intervals after tumor cell inoculation. Circulating levels of anti-p15E and, if possible, p15E itself will be monitored during the course of the experiments. We will continue our studies to determine circulating p15E levels in tumor-bearing mice and whether the levels of p15E correlate with tumor growth or metastasis. We will continue to use our competition ELISA assay to make these determinations, but during the next year we will attempt to determine what our loweat level of sensitivity will be using this assay. In addition, using p15E obtained by recombinant DNA technology we will attempt to develop new highly sensitive RIA and EIA assays for p15E. Using synthetic peptides corresponding to portions of the p15E protein, such as that region we have recently shown to be homologous to the envelope protein gp21E of HTLV, we will determine the mechanisms of p15E-mediated immunosuppression. We will also use such synthetic peptides to produce specific antibodies to defined regions of the p15E protein. (IS)