Feline leukemia virus (FeLV)-induced lymphosarcoma in cats is a unique model to study the immune mechanisms involved in the initiation and progression or dimunition of neoplastic cell growth. We have shown that FeLV-infected cats with lymphosarcoma are hypocomplementemic and that their sera contain high levels of circulating immune complexes (CICs). We also demonstrated that 50% of the FeLV-infected cats with leukemia-lymphoma complex treated by ex vivo immunoadsorption using Staphylococcal Protein A filters showed dramatic tumor regression, including disappearance of tumor cells and virus from the circulation. More recently, we have shown that injection of purified Staphylococcal Protein A intraperitoneally into FeLV-infected cats with leukemia-lymphosarcoma also caused regression of tumor with loss of viremia. A consistent finding in all of the cats responding to Protein A therapy was the appearance during treatment of dramatic transient increases of gamma interferon followed with increasing levels of cytotoxic antibody and loss of viremia. In contrast, interferon levels of cats not responding to treatment, or normal cats treated in an identical manner, did not have increased levels of interferon. Using monoclonal antibodies, the cytotoxic antibody was shown to be directed against gp70, a glycoprotein of Mr 70,000, of FeLV. These data suggest that interferon and cytotoxic antibody may play an important role in inducing remission of leukemia and loss of viremia in cats treated with Staphylococcal Protein A. We are isolating and purifying cat interferon and cytotoxic antibody and studying the mechanisms in depth both in vivo and in vitro of the role of antibody and interferon in the destruction of tumor cells. Results of these studies will lead to a greater understanding of the interplay between the immune system, interferon, and neoplasia and are thus directly applicable to human cancer. (HF)