We have injected purified Staphylococcus aureus protein A intraperitoneally into leukemic cats infected with feline leukemia virus, into cats persistently infected with feline leukemia virus but without hematologic or cytologic abnormalities, and into healthy cats without feline leukemia virus infection. Pre-and post-treatment serum samples were evaluated sequentially for interferon activity and for complement-dependent cytotoxic antibody. Our results indicate that serum interferon increased dramatically (<3 to 324 units/ml) during treatment only in cats that responded to staphylococcal protein A therapy. Increase of interferon preceded or was closely associated with increasing levels of cytotoxic antibody, loss of viremia, and correction of cytological and hematological abnormalities of three leukemic cats. The cytotoxic antibody was shown to be specific for envelope glycoprotein gp7O of the feline leukemia virus. One persistently feline leukemia virus-infected cat without leukemia that became nonviremic also developed high levels of interferon and specific cytotoxic antibody. By contrast, interferon levels of cats not responding to treatment had levels of <3 to 27 units/ml. Normal healthy cats injected with staphylococcal protein A showed moderate transient increases of interferon but no detectable cytotoxic antibodies to FL-74 cells. These data suggest that interferon and cytotoxic antibody may play important, possibly complementary roles in inducing remission of leukemia and loss of viremia in cats treated with staphylococcal protein A.Remission of leukemia-lymphoma associated with disappearance of feline leukemia virus (FeLV) (4,5), IFN activity and complementdependent cytotoxic antibody were studied in sera of several cats that had been injected i.p. with SPA. It will be shown that regression of malignancy and loss of evidence of virus infection occurred in cats that experienced first an increase in IFN that was followed by appearance and usually progressive increase of a complement-dependent cytotoxic antibody directed against a virus-infected feline lymphoma cell line. MATERIAL AND METHODSAnimals. Pet cats were selected for treatment by ex vivo immunoadsorption (2, 3) or by injection with purified SPA (Pharmacia, Uppsala, Sweden). The SPA injections were given i.p. (20 pug/2.75 kg of body weight) twice weekly for 10-12 weeks. Bone marrow and peripheral blood smears were evaluated prior to treatments and after every 10th treatment. FeLV status was determined biweekly by indirect immunofluorescence assay (IFA) (6) and enzyme-linked immunosorbent assay (ELISA) as described (2). Pre-and posttreatment serum samples were stored at -70'C until assayed for IFN and cytotoxic antibody.Feline IFN Assay. Feline IFN was assayed by a modification of the microplaque reduction method (7), using approximately 40 plaque-forming units (pfu) of vesicular stomatitis virus (VSV) per well on FFC-9 cells (fetal cat fibroblast cell line kindly provided by N. C. Pedersen, University of California, Davis). An IFN concen...

Fifty cats with feline leukemia virus (FeLV) infection and leukemia-lymphoma complex were treated by ex vivo immunoadsorption with Staphylococcus protein A-bound filters. Most cats responded to therapy. Twelve showed tumor regression, including disappearance of tumor cells, but died later of other complications. Three have had long-term remission of more than 1 year and remain healthy. A consistent finding in these three cats was the appearance during treatment of a complement-dependent cytotoxic antibody against cat lymphoma cells (FL-74). The cytotoxic antibody increased substantially during treatment. Appearance and increase of the cytotoxic antibody was associated with disappearance of FeLV from blood and remission of leukemia. By electroblot analysis, antibody to FeLV protein (Mr, 70,000) was detected in serum prior to detection of the cytotoxic antibody. The cytotoxic antibody was found by immunofluorescence to be specific for antigens on membranes of viable FL-74 cells. By using monoclonal antibodies to FL-74 cells and to components of FeLV, the cytotoxic antibody was shown to be directed against gp70, a glycoprotein of Mr 70,000, but not against p27 of FeLV or other membrane antigen(s) of FL-74 cells. The development of a high concentration of cytotoxic antibody to FeLV gp7O may play an important role in tumor regression and in disappearance of FeLV infection.Ex vivo immunoadsorption by Staphylococcus protein A (SPA) for treatment of cancer has aroused interest because tumor regression and immunostimulation have been observed by several investigators (1-4). Feline leukemia virus (FeLV)-induced neoplasms (e.g., lymphosarcoma or leukemia) offer excellent models for the study of these phenomena. Tumor regression has been produced in a significant number of cats treated in our laboratory by ex vivo immunoadsorption using SPA over the last 4 years (5-7). Similar tumor regression had been observed previously (8)

A new feline lymphoma-derived cell line, designated BKD, was isolated from an anterior mediastinal tumor. Cells of this line were characterized as lymphoid based on morphology, the lack of intracellular esterase and peroxidase activity, and absence of phagocytic function. In contrast with other established feline lymphoma-derived cell lines, cells of the BKD line lack characteristics of both feline T-cells and B-cells in that they neither form rosettes with guinea pig erythrocytes nor have demonstrable surface or cytoplasmic immunoglobulin. Approximately one third of BKD cells form EAC rosettes, a significant number of rosette forming cells (p = 0.0001) when compared to background sheep E-rosetting activity. In addition, a consistently titratable level of interleukin-2-like activity was produced when BKD cells were coincubated with concanavalin A and phorbol-12-myristate-13-acetate. Chromosome analysis showed that a majority of BKD cells are diploid. This new cell line has been continuously replicating in culture for over one year and produces feline leukemia virus as demonstrated by several analyses.

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