Based on our studies, we developed a diagnostic kit for evaluating and monitoring the status of the immune system prior to and following immunotherapy/drug treatment in chronic diseases. Patients living with chronic diseases, such as diabetes, arteriosclerosis, IBD, rheumatoid arthritis, infections and cancer often suffer from complications that could be foretold by changes in the function of the immune system, such as chronic inflammation and associated immunosuppression. In addition, many respond poorly to a chosen immunotherapy, thus further aggravating their condition. Currently, prognosis of immunotherapy success rates or complication appearance in these patients is done retrospectively, since there are no available prognostic/diagnostic tools to predict the harmful immune status and to follow up effects of given treatments. We identified a novel biomarker, CD247, for distinguishing between acute and chronic inflammation, detecting the immune status in patients suffering from diseases characterized by chronic inflammation, and monitoring the efficacy of a given therapy.
Based on this discovery, we developed a prognostic/diagnostic kit, utilizing a simple assay analyzing a whole blood sample for monitoring the immune status prior to and following treatment. This kit will enable an intelligent selection of the timing and drug/immunotherapeutic treatment (personalized treatment), improving the efficacy of a given immunotherapy to patients with chronic diseases. Better diagnosis and prognosis of the immune status should dramatically increase quality of life and decrease the high expenses needed for treating complications characterizing late stages of chronic disease. The advantages of the novel kit were established both by results in animal models, and in preliminary trials with diabetic patients. We are currently:
These studies will shed light on the basic mechanisms that control receptor expression, transport and function, as well as contribute to the development of immunotherapeutic strategies for immunosuppression associated with chronic inflammatory diseases.
Baniyash, M., Netanel, T., and Witz, I.P. (1981) Differences in cell density associated witt differences in lung-colonizing ability of B16 melanoma cells. Cancer Res. 41: 433-437.
Baniyash, M., Smorodinsky, N.I., Yaakubovicz, M., and Witz, I.P. (l982) Serologically-detectable MHC and tumor associated antigens on B16 melanoma variants and humoral immunity in mice bearing these tumors. J. Immunol. 129: 1318-1323.
Ballin, A., Aldjem, M., Baniyash, M., Boichis, H., Barzilay, Z., Gal, R., and Witz, I.P. (1983) The effect of Lithium Chloride in tumor appearance and survival of melanoma bearing mice. Br. J. Cancer 48: 83-87.
Baniyash, M., and Eshhar, Z. (1984) Monoclonal antibodies to murine IgE inhibit IgE binding to rat basophilic leukemia cells. Eur.J.Immunol. 14: 799-807.
Baniyash, M., Eshhar, Z., and Rivnay, B. (1986) Interrelation between antigenic sites on IgE recognized by monoclonal anti-IgE antibodies and the mast cell receptor. J. Immunol. 136: 588-593.
Baniyash, M., Alkalay, I., and Eshhar, Z. (1987) Monoclonal antibodies specific to the alpha chain of mast cells Fc-epsilon receptor. J.Immunol. 138: 2999-3004.
Baniyash, M., and Eshhar, Z. (1987) Anti-anti-IgE idiotypic antibodies mimic IgE in its binding to the Fc-epsilon receptor. Eur. J. Immunol. 17: 1337-1341.
Baniyash, M., Eshhar, Z., and Khery, M. (1988) Anti-IgE monoclonal antibodies directed at the Fc-epsilon-receptor binding site. Mol. Immunol. 25: 705-711.
Weissman, A.M., Baniyash, M., Hou, D., Samelson, L.E., and Klausner, R.D. (1988) Disulfide linkage of the zeta and eta chains of the T cell antigen receptor. Science 239: 1018-1021.
Baniyash, M., Garcia-Morales, P., Bonifacino, J.S., Samelson, L.E., and Klausner, R.D. (1988) Disulfide linkage of the zeta and eta chains of the T cell receptor: Possible identification of two structural classes of receptors. J. Biol. Chem. 263: 9874-9878.
Baniyash, M., Garcia-Morales, P., Luong, E., Samelson, L.E., and Klausner, R.D. (1988) The T cell antigen receptor zeta chain is tyrosine phosphorylated upon activation. J. Biol. Chem. 263:18225-18230.
Sharon, M., Gnarra, J.R., Baniyash, M., and Leonard, W.J. (l988) Possible association between IL2 receptors and class I HLA molecules on T cells. J. Immunol. 141: 3512-3515.
Klausner, R.D., Weissman, A.M., Baniyash, M., Bonifacino, J.S. and Samelson, L.E. (l989) The role of the zeta chain in expression, structure and function of the T cell receptor. Adv. Exp. Med. Biol. 254: 21-24.
Baniyash, M., Hsu, V.W., Seldin, M.F., and Klausner, R.D. The isolation and characterization of the murine T cell antigen receptor zeta chain gene. (1989) J. Biol. Chem., 264: 13252-13257.
Hsu, V.W., Klausner, R.D., Fine, J.S., Kruisbeek, A.M., and Baniyash, M. (1992) Changes in the methylation pattern of the TCR zeta chain gene correlate with its expression in T cells and developing thymocytes. The New Biologist, 4: 166-171.
Caplan, S., Zeliger, S., Wang, L., and Baniyash, M. (1995) Cell surface expressed T cell antigen receptor zeta chain is associated with the cytoskeleton. PNAS, 92: 4768-4772.
Messika, E.J., Yefenof, E., Gallily, R., Avni, O., and Baniyash, M. (1995) Identification and characterization of a novel protein associated with macrophage CR3. J. Immunol., 154: 6564-6570.
Wang, L., Bronstein, N., Hsu, V. and Baniyash, M. (1995) Transcriptional regulation of the murine TCR gene. Int. Immunol., 7:1627-1635.
Caplan, S. and Baniyash, M. (1995) Multisubunit receptor complexes in the immune system and their association with the cytoskeleton in search of functional significance. Invited review for Immunologic Research, 14:98-118.
Caplan, S. and Baniyash, M. (1996) Normal T cells express two TCR populations, one of which is linked to the cytoskeleton via chain and displays a unique activation-dependent phosphorylation pattern. J. Biol. Chem., 271:20705-20712.
Palumbo, G. A., Yarom, N., Gazit, A., Sandalon, Z., Baniyash, M., Kleinberger-Doron, N., Levitzki, A., Ben-Yehuda, D. (1997) The Tyrphostin AG17 Induces Apoptosis and Inhibition of cdk2 Activity in a Lymphoma Cell Line That Overexpresses bcl-2. Cancer Res., 37, 2434-2439.
Bishara, A., Aker, A., Amar, A., Brautbar, C., Schlesinger, M., Rabinowitz, R., Slavin, S., and Baniyash, M. (1998) Enhanced lymphoid cell recovery of an immunodeficient child following bone marrow transplantation: Correlation with the presence of costimulatory antibodies in the serum. Exp. Hematol., 26: 580-587.
Avni, O., Pur, Z., Yefenof ,E., and Baniyash, M. (1998) Complement receptor 3 (CR3) of macrophages is associated with galectin-1-like protein. J. Immunol., 160: 6151-6158.
Bronstein-Sitton, N., Wang, L., Cohen, L., and Baniyash, M. (1999) Expression of the TCR chain following activation is controlled at distinct checkpoints: implications for cell surface. J. Biol. Chem. 274: 23659-23665.
Caplan, S., and Baniyash, M. (2000) Searching for significance in TCR-cytoskeleton interactions. Immunology Today 21:223-228.
Caplan, S., Almogi-Hazan, O., Ezernitchi, A., Manaster, E., Gazit, A., and Baniyash, M. (2001) The cytoskeleton-associated TCR chain is constitutively phosphorylated in the absence of an active p56(lck) form. Eur J Immunol. 31:580-589.
Villa, A., Sobacchi, C., Notarangelo, LD., Bozzi, F., Abinun, M., Abrahamsen, TG., Arkwright, PD., Baniyash, M., Brooks, EG., Conley, ME., Cortes, P., Duse, M., Fasth, A., Filipovich, AM., Infante, AJ., Jones, .A, Mazzolari, E., Muller, SM., Pasic, S., Rechavi, G., Sacco, MG., Santagata, S., Schroeder, ML., Seger, R., Strina, D., Ugazio, A., Valiaho, J., Vihinen, M., Vogler, LB., Ochs, H., Vezzoni, P., Friedrich, W., and Schwarz, K. (2001) V(D)J recombination defects in lymphocytes due to RAG mutations: severe immunodeficiency with a spectrum of clinical presentations. Blood. 97:81-88.
Mostoslavsky, G., Fischel, R., Yachimovich, N., Yarkoni, Y., Rosenmann, E., Monestier, M., Baniyash, M., and Eilat, D. (2001) Lupus anti-DNA autoantibodies cross-react with a glomerular structural protein: a case for tissue injury by molecular mimicry. Eur J Immunol. 31:1221-7.
Bronstein-Sitton N., Cohen-Daniel L., Vaknin I., Ezernitchi AV., Leshem B., Halabi A., Houri-Hadad Y., Greenbaum E., Zakay-Rones Z., Shapira L., and Baniyash M. (2003). Sustained exposure to bacterial antigen induces IFNg-dependent T cell antigen receptor z down-regulation and impaired T cell function. Nat. Immunol. 4:957-964.
Gonen-Gross, T., Achdout, H., Gazit, R., Hanna, J., Mizrahi, S., Markal, G., Goldman-Wohl, D., Yagel, S., Horejsi, V., Levy, O., Baniyash, M., and Mandelboim, O. (2003). Complexes of HLA-G protein on the cell surface are important for the LIR-1 function. J. Immunol. 171:1343-5.
Baniyash M. (2004). Down-regulation of the TCRz chain: curtailing an excessive inflammatory immune response. Invited review for Nat. Immunol. Rev. 4:675- 687.
Baniyash M. (2006). The inflammation-cancer linkage: A double-edged sword? Semin. Cancer Biol. 16:1-2. An editorial chapter as a guest editor of a volume in Seminars in Cancer Biology entitled “A double-edged sword?”
Baniyash M. (2006). Chronic inflammation, immunosuppression and cancer: New insights and outlook. Semin. Cancer Biol. 16:80-88.
Ezernitchi, AV., Vaknin, I., Cohen-Daniel, L., Levy, O., Manaster, E., Halabi, A., Pikarsky, E., Shapira, L., Baniyash, M. (2006). TCR zdown-regulation under chronic inflammation is mediated by myeloid suppressor cells differentially distributed between various lymphatic organs. J Immunol. 177:4763-72.
Marhaba, R., Vitacolonna, M., Hildebrand, D., Baniyash, M., Freyschmidt-Paul, P., Zoller, M. (2007). The importance of myeloid-derived suppressor cells in the regulation of autoimmune effector cells by a chronic contact eczema. J Immunol. 179:5071-81.
Einstein, O., Fainstein, N., Vaknin, I., Mizrachi-Kol, R., Reihartz, E., Grigoriadis, N., Lavon, I., Baniyash, M., Lassmann, H., Ben-Hur, T. (2007). Neural precursors attenuate autoimmune encephalomyelitis by peripheral immunosuppression. Ann Neurol. 61:209-18.
Vaknin, I., Blinder. L., Wang, L., Gazit, R., Shapira, E., Genina, O., Pines, M., Pikarsky, E., Baniyash, M. (2008). A common pathway mediated through Toll-like receptors leads to T- and natural killer-cell immunosuppression. Blood. 111:1437-47.
Fainstein, N., Vaknin, I., Einstein, O., Zisman, P., Ben Sasson, S.Z., Baniyash, M., Ben-Hur, T. (2008). Neural precursor cells inhibit multiple inflammatory signals. Mol Cell Neurosci. 39:335-41.
Silberman, I., Sionov, R.V., Zuckerman, V., Haupt, S., Goldberg, Z., Strasser, A., Ben-Sasson, Z.S., Baniyash, M., Koleske, A.J., Haupt, Y. (2008). T cell survival and function requires c-Abl tyrosine kinase. Cell Cycle. 7:3847-57.
Meyer, C., Sevko, A., Ramacher, M., Bazhin, AV., Falk, CS., Osen, W., Borrello, I., Kato, M., Schadendorf, D., Baniyash, M., Umansky, V. (2011) Proc Natl Acad Sci U S A. 108:17111-6.
Kanterman, J., Sade-Feldman, M., and Baniyash, M. New insights into chronic inflammation-induced immunosuppression. (2012) Seminars in cancer biology. 22:307-18 (Invited review).
Sevko, A., Sade-Feldman, M., Kanterman, J., Michels, T., Falk, CS., Umansky, L., Ramacher, M., Kato, M., Schadendorf, D., Baniyash, M., and Umansky, V. Cyclophosphamide Promotes Chronic Inflammation-Dependent Immunosuppression and Prevents Antitumor Response in Melanoma. (2012) J Invest Dermatol. [Epub ahead of print]
Sade-Feldman, M., Kanterman, J., Ish-Shalom, E., Elnekave, M., Horwitz, E., and Baniyash, M. TNF blocks differentiation and enhances suppressive activity of immature myeloid cells during chronic inflammation. (2013) Immunity, (Accepted for publication).