Drug – bio-affecting and body treating compositions – Lymphokine – Interferon
Patent
1995-05-08
1998-03-17
Bleutge, John C.
Drug, bio-affecting and body treating compositions
Lymphokine
Interferon
424 854, 530351, A61K 3766
Patent
active
057283788
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention concerns a pharmaceutical preparation or system for activation of natural killer cells (NK-cells), in order for example, to treat tumors or virus infections.
BACKGROUND OF THE INVENTION
Natural killer cells (NK-cells) are a group of spontaneously cytotoxic lymphocytes that destroy tumor cells by lysis with no antigen specificity or restriction by histocompatibility molecules. Monocytes are involved in the regulation of the NK-cell's function, both through mechanisms involving cell contact and through providing soluble NK cell-regulating mediators. Recently, a cell contact-mediated mechanism has been described whereby monocytes regulate NK-cells. This type of monocyte-mediated regulation is exerted by monocytes that are obtained directly from peripheral blood through counterflow centrifugal elutriation (CCE) and is regulated by the biogenic amines histamine and serotonin (Hellstrand and Hermodsson, 1986, J. Immunol. 137, 656-660; Hellstrand and Hermodsson, 1987, J. Immunol. 139, 869-875; Hellstrand and Hermodsson, 1990, Scand. J. Immunol. 31, 631-645; Hellstrand and Hermodsson, 1990, Cell. Immunol. 127, 199-214; Hellstrand, Kjellson and Hermodsson, 1991, Cell. Immunol., 138, 44-54). These NK-cell regulating mechanisms caused by biogenic amines should be of importance to the NK cell-mediated defence against metastatic tumors in vivo (Hellstrand, Asea and Hermodsson (1990), J. Immunology 145, 4365-4370).
Interferon-.alpha. (IFN-.alpha.) is an important regulating factor for NK cells. It effectively enhances the NK cell's cytotoxicity (NKCC) both in vivo and in vitro (Trinchieri, 1989, Adv. immunol. 47, 187-376; Einhorn, Blomgren and Strander, 1978, Int. J. Cancer 22, 405-412; Friedman and Vogel, 1984, Adv. Immunol., 34, 97-140).
Owing to the high rate of cancer and the only partially successful treatment methods available today, there is a constant demand for other improved methods of treatment of tumors. There is also a great demand for improved treatment methods for virus infections.
SUMMARY OF THE INVENTION
The goal of the invention is to create a pharmaceutical preparation or system that effectively stimulates NK cells, e.g., in order to treat tumors, primarily myelomas, renal cancer, leukemias and melanoma, or to treat virus infections, primarily chronic hepatitis B and hepatitis C. The preparation or system according to the invention involves a first composition, containing interferon-.alpha. or analogues thereof, and a second composition containing at least one substance with histamine H.sub.2, or serotonin 5-HT.sub.1A- receptor agonist activity, whereby said first and second compositions are either mixed in a preparation or supplied in separate doses in an amount sufficient for the intended treatment. The invention also comprises a method for treatment of viral or neoplastic disease comprising the step of coadministering to an animal, including a human, an effective amount of a histamine H.sub.2 receptor agonist or a secotonin 5-HT.sub.1A receptor agonist. Furthermore, the invention includes use of a histamine H.sub.2 receptor agonist or a 5-HT.sub.1A receptor agonist in the preparation of a medicament for treatment of viral or neoplastic disease by coadministration with interferon-.alpha., as well as the use of interferon-.alpha. in the preparation of a medicament for treatment of neoplastic or viral disease by coadministration with a histamine H.sub.2 receptor agonist or a serotonin 5-HT.sub.1A receptor agonist.
The invention shall be described in greater detail below, making reference to reported in vitro experiments.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows in graph form the synergistic NK cell activation against cultured target cells produced by IFN-a and histamine or serotonin for various concentrations of IFN-.alpha. (0-100 U/ml). FIG. 2 shows in graph form the synergistic NK cell activation produced against freshly recovered human leukemic cells by IFN-.alpha. and histamine for various concentrations of IFN-.alpha. (0-100 U/ml).
DE
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"Enhancement of Human Natural Killer Cell Function by the Combined Effects of Tumor Necrosis Factor .alpha. or Interleukin-1 a
Hellstrand Kristoffer
Hermodsson Svante
Bleutge John C.
Harrison Robert H.
Maxim Pharmaceuticals, Inc.
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