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). Our studies indicate that the complexes contain FeLV and IgG. Both FeLV and FeLV-containing complexes were shown to activate feline complement (C) in vitro. However, feline C is inhibitory for C-mediated cell lysis including intermediate sheep cells, FeLV, and a leukemic feline cell line, FeLV-74. More recently, in in vivo studies of an extracorporeal immunosorption procedure using Staphylococcus aureus or purified Staph protein A bound to filters to treat leukemic cats, we have observed a dramatic remission of the tumor and clinical improvement in the treated animals. Complete remission is observed in more than 90% of aleukemic leukemic cats and a partial remission in cats that normally do not recover. The remission was associated with increasing levels of feline gamma-interferon, C-mediated cytotoxic antibody levels, drop in FeLV antigen (gp70) using a monoclonal antibody prepared in our laboratory, and a drop in CICs. We propose to isolate and purify cat interferon, cytotoxic C-dependent antibody, and study the mechanisms in depth both in vivo and in vitro of the role of antibody in the destruction of tumor cells. In order to rule out any leaching of Protein A from the columns, we have also begun to inject purified Protein A intravenously using leukemic cats. We will include the above parameters in sera of these cats as well. (HF)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA040931-02
Application #
3181252
Study Section
Experimental Immunology Study Section (EI)
Project Start
1985-02-01
Project End
1987-03-31
Budget Start
1985-07-01
Budget End
1987-03-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of South Florida
Department
Type
Schools of Medicine
DUNS #
City
Tampa
State
FL
Country
United States
Zip Code
33612
Haraguchi, Soichi; Good, Robert A; Day-Good, Noorbibi K (2008) A potent immunosuppressive retroviral peptide: cytokine patterns and signaling pathways. Immunol Res 41:46-55
Haraguchi, S; Good, R A; Cianciolo, G J et al. (1997) Immunosuppressive retroviral peptides: immunopathological implications for immunosuppressive influences of retroviral infections. J Leukoc Biol 61:654-66
Kraus, L A; Bradley, W G; Engelman, R W et al. (1996) Relationship between tumor necrosis factor alpha and feline immunodeficiency virus expressions. J Virol 70:566-9
Bradley, W G; Kraus, L A; Good, R A et al. (1995) Dehydroepiandrosterone inhibits replication of feline immunodeficiency virus in chronically infected cells. Vet Immunol Immunopathol 46:159-68
Bradley, W G; Ogata, N; Good, R A et al. (1994) Alteration of in vivo cytokine gene expression in mice infected with a molecular clone of the defective MAIDS virus. J Acquir Immune Defic Syndr 7:1-9
Bush, K; Day, N K; Kraus, L A et al. (1994) Molecular cloning of feline interleukin 12 p35 reveals the conservation of leucine-zipper motifs present in human and murine IL-12 p35. Mol Immunol 31:1373-4
James-Yarish, M; Bradley, W G; Emmanuel, P J et al. (1994) Detection of cell specific cluster determinant expression by reverse transcriptase polymerase chain reaction. J Immunol Methods 169:73-82
Ogata, N; Day, N K; Buell, R D et al. (1993) Detection of the MAIDS virus using the polymerase chain reaction. PCR Methods Appl 2:272-4
Bradley, W G; Gibbs, C; Kraus, L et al. (1993) Molecular cloning and characterization of a cDNA encoding feline interleukin-6. Proc Soc Exp Biol Med 204:301-5
Haraguchi, S; Good, R A; Cianciolo, G J et al. (1993) Transcriptional down-regulation of tumor necrosis factor-alpha gene expression by a synthetic peptide homologous to retroviral envelope protein. J Immunol 151:2733-41

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