Abstract
Interleukin-12 (IL-12) is a recently cloned cytokine (1,2) that has some unique properties. Two groups working independently simultaneously discovered this cytokine utilizing different assay systems. One group was searching for a cytokine, initially called cytotoxic lymphocyte maturation factor (CLMF) that synergized with IL-2 in the induction of several cytotoxic lymphocyte populations (3–5). The second group was characterizing a cytokine, natural killer cell stimulatory factor (NKSF), that enhanced natural killer (NK) cell activity and induced the secretion of interferon gamma (IFN-γ) from these cells (6). It is now clear that both of these properties, as well as others, are associated with one cytokine, IL-12.
Chapter PDF
References
Gubler, U., Chua, A.O., Schoenhaut, D.S., et al. Coexpression of two distinct genes is required to generate secreted, bioactive cytotoxic lymphocyte maturation factor. Proc Natl Acad Sci USA 88: 4143–4147, 1991.
Wolf, S.A., Temple, P.A., Kobayashi, M., et al. Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells. J Immunol 146: 3074–3081, 1991.
Gately, M.K., Wilson, D.E., Wong, H.L. Synergy between recombinant interleukin 2 (rIL2) and IL 2-depleted lymphokine-containing supernatants in facilitating allogeneic human cytolytic T lymphocyte responses in vitro. J Immunol 136: 1274–1282, 1986.
Wong, H.L., Wilson, D.E., Jenson, J.C., Familletti, P.C., Stremlo, D.L., Gately, M.K. Characterization of a factor(s) which synergizes with recombinant interleukin 2 in promoting allogeneic human cytolytic T-lymphocyte responses in vitro. Cell Immunol 111: 39–54, 1988.
Stern, A.S., Podlaski, F.J., Hulmes, J.D., et al. Purification to homogeneity and partial characterization of cytotoxic lymphocyte maturation factor from human Blymphoblastoid cells. Proc Natl Acad Sci USA 87: 6808–6812, 1990.
Kobayashi, M., Fitz, L., Ryan, M., et al. Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biological effects on human lymphocytes. J Exp Med 170: 827–845, 1989.
Mule, J.J., Yang, J.C., Lafreniere, R., Shu, S., and Rosenberg, S.A. Identification of cellular mechanisms operational in vivo during the regression of established pulmonary metastases by the systemic administration of high-dose recombinant interleukin 2. J Immunol 139: 285–294, 1987.
Brunda, M.J., Sulich, V.,and Bellantoni, D. The anti-tumor effect of recombinant interferon alpha or gamma is influenced by tumor location. Int J Cancer 40: 807–810, 1987.
Kedar, E., and Klein, E. Cancer immunotherapy: Are the results discouraging? Can they be improved? Adv Cancer Res 59: 245–322, 1992.
Baron, S., Tyring, S.K., Fleischmann, W.R., Jr., et al. The interferons. Mechanism of action and clinical application. JAMA 266: 1375–1383, 1991.
Rosenberg, S.A., Lotze, M.T., Muul, L.M., et al. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Eng J Med 316: 889–897, 1987.
Sieburth, D., Jabs, E.W., Warrington, J.A., et al. Assignment of genes encoding a unique cytokine (IL12) composed of two unrelated subunits to chromosomes 3 and 5. Genomics 14: 59–62, 1992.
Podlaski, F.J., Nanduri, V.B., Hulmes, J.D., et al. Molecular characterization of interleukin- 12. Arch Biochem Biophys 294: 230–237, 1992.
Schoenhaut, D.S., Chua, A.O., Wolitzky, A.G., et al. Cloning and expression of murine IL-12. J Immunol 148: 3433–3440, 1992.
Chizzonite, R., Truitt, T., Desai, B.B., et al. IL-12 receptor. I. Characterization of the receptor on phytohemagglutinin-activated human lymphoblasts. J Immunol 148: 3117–3124, 1992.
Desai, B.B., Quinn, P.M., Wolitzky, A.G., Mongini, P.K.A., Chizzonite, R., and Gately, M.K. IL-12 receptor. II. Distribution and regulation of receptor expression. J Immunol 148: 3125–3132, 1992.
Gately, M.K., Gubler, U., Brunda, M.J., et al. Interleukin-12: a cytokine with therapeutic potential in oncology and infectious diseases. Ther Immunol. In press.
Chua, A.O., Chizzonite, R., Desai, B.B., et al. Expression cloning of a human IL-12 receptor component: a new member of the cytokine receptor superfamily with strong homology to gp130. J Immunol, In press.
D’Andrea, A., Rengaraju, M., Valiante, N.M., et al. Production of natural killer cell stimulatory factor (interleukin-12) by peripheral blood mononuclear cells. J Exp Med 176, 1387–1398, 1992.
Brunda, M.J. Interleukin-12. J Leuk Biol 55: 280–288, 1994.
Tripp, C.S., Wolf, S.F., and Unanue, E.R. Interleukin 12 and tumor necrosis factor are costimulators of interferon production by natural killer cells in severe combined immunodeficiency mice with listeriosis, and interleukin 10 is a physiologic antagonist. Proc Natl Acad Sci USA 90: 3725–3729, 1993.
Gazzinelli, R.T., Hieny, S., Wynn, T.A., Wolf, S., and Sher, A. Interleukin 12 is required for the T-lymphocyte-independent induction of interferon by an intracellular parasite and induces resistance in T-cell-deficient hosts. Proc Natl Acad Sci USA 90: 6115–6119, 1993.
Hsieh, C.-S., Macatonia, S.E., Tripp, C.S., Wolf, S.F., O’Garra, A., and Murphy, K.M. Development of TH1 CD4` T cells through IL-12 produced by Listeria-induced macrophages. Science 260: 547–549, 1993.
Gately, M.K., Wolitzky, A.G., Quinn, P.M, Chizzonite, R. Regulation of human cytolytic lymphocyte responses by interleukin-12. Cell Immunol 143: 127–142, 1992.
Robertson, M.J., Soiffer, R.J., Wolf, S.F., et al. Responses of human natural killer (NK) cells to NK cell stimulatory factor (NKSF): cytolytic activity and proliferation of NK cells are differentially regulated by NKSF. J Exp Med 175: 779–788, 1992.
Chehimi, J., Valiante, N.M., D’Andrea, A., et al. Enhancing effect of natural killer cell stimulatory factor (NKSF/interleukin-12) on cell-mediated cytotoxicity against tumor-derived and virus-infected cells. Eur J Immunol 23: 1826–1830, 1993.
Gately, M.K., Warner, R.R., Honasoge, S., et al. Administration of recombinant IL-12 to normal mice enhances cytolytic lymphocyte activity and induces production of IFN’y in vivo. Int Immunol 6: 157–167, 1994.
Hendrzak, J.A., Chizzonite, R., Gately, M.K., and Brunda, M.J. Tumoricidal activation of murine peritoneal macrophages by interleukin-12. Submitted for publication.
D’Andrea, A., Aste-Amezaga, M., Valiante, N.M., Ma, X., Kubin, M., and Trinchieri, G. Interleukin 10 (IL-10) inhibits human lymphocyte interferony production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells. J Exp Med 178: 1041–1048, 1993.
Naume, B., Gately, M.K., and Espevik, T. A comparative study of IL-12 (cytotoxic lymphocyte maturation factor), IL-2-, and IL-7-induced effects on immunomagnetically purified CD56+ NK cells. J Immunol 148: 2429–2436, 1992.
Morris, S.C., Madden, K.B., Adamovicz, J.J., et al. Effects of interleukin-12 on in vivo cytokine gene expression and Ig isotype selection. J Immunol 152: 1047–1056, 1994.
Manetti, R., Parronchi, P., Giudizi, M.G., et al. Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Thl)-specific immune response and inhibits the development of IL-4-producing Th cells. J Exp Med 177: 1199–1204, 1993.
Brunda, M.J., Luistro, L., Warner, R.R., Wright, R.B., Hubbard, B.R., Murphy, M., Wolf, S.F., and Gately, M.K. Antitumor and antimetastatic activity of interleukin-12 against murine tumors. J Exp Med 178: 1223–1230, 1993.
Stern, L.L., Tarby, C.M., Tamborini, B., and Truitt, G.A. Preclinical development of IL-12 as an anticancer drug: comparison to IL-2. Proc Am Assoc Cancer Res. 35:520
Nastala, C.L., Edington, H.D., McKinney, T.G., Brunda, M.J., Tahara, H., Nalesnki, M., Brunda, M.J., Gately, M.K., Wolf, S.F., Schreiber, R., Stewart, T., Storkus, W.J., and Lotze, M.T. Recombinant interleukin-12 administration induces tumor regression in association with interferon-gamma production. J Immunol 153: 1697–1706, 1994.
Brunda, M.J., Luistro, L., Hendrzak, J.A., Fountalakis, M., Garotta, G., and Gately, M.K. Interferon gamma is necessary but not sufficient to mediate the antitumor effect of interleukin-12. Submitted for publication.
O’Toole, M., Wolf, S.F., O’Brien, C., Hubbard, N, and Herrmann, S. Effect of in vivo IL-12 administration on murine tumor cell growth. J Immunol 150: 294A, 1993.
Tahara, H., Zeh, H., III, Storkus, W.J., et al. Fibroblasts genetically engineered to secrete interleukin-12 can suppress tumor growth in vivo and induce anti-tumor immunity to a murine melanoma. Cancer Res 54: 182–189, 1994.
Truitt, G.A., Bontempo, J.M., Stern, L.L., et al. Efficacy and toxicity elicited by recombinant interferons alpha and gamma when administered in combination to tumor-bearing mice. Biotech Therapeutics 1, 1–16, 1989.
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 1995 Springer-Verlag New York Inc.
About this paper
Cite this paper
Brunda, M.J., Luistro, L., Hendrzak, J.A., Fountoulakis, M., Garotta, G., Gately, M.K. (1995). Interleukin 12: Biology and Preclinical Studies of a New Anti-Tumor Cytokine. In: Biology of Renal Cell Carcinoma. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-2536-2_16
Download citation
DOI: https://doi.org/10.1007/978-1-4612-2536-2_16
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4612-7571-8
Online ISBN: 978-1-4612-2536-2
eBook Packages: Springer Book Archive