Chemistry: molecular biology and microbiology – Animal cell – per se ; composition thereof; process of... – Primate cell – per se
Patent
1992-09-29
1999-12-14
Fitzgerald, David L.
Chemistry: molecular biology and microbiology
Animal cell, per se ; composition thereof; process of...
Primate cell, per se
435 695, 4353201, 435325, 435360, 4352542, 530351, 530327, 530326, 530325, 530324, 536 2351, 514 2, 514 14, 514 13, 514 12, 424 851, C12N 1519, C07K 1452
Patent
active
060016493
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention relates to a novel protein having a cytokinin-type activity, to the genetic engineering tools for its production, namely a recombinant DNA, an expression vector carrying this recombinant DNA, and the procaryotic microorganisms and the eucaryotic cells containing this recombinant DNA, and to a drug, useful especially as an anticancer agent or immunomodulator, in which this protein is present as the active principle.
It is well known that the immune system comprises cellular elements and soluble substances, called cytokinins, secreted by said elements. Cytokinins are proteins which effect communication between an emitter cell and a target cell belonging either to the immune system or to another biological system of the organism. In general, cytokinins have a so-called pleiotropic biological activity, i.e. they can have multiple effects on the target cell: proliferation, differentiation, cytolysis, activation, chemotaxis etc. Several of these molecules have already found applications in therapeutics: for example, interleukin-2 or interferon-.alpha. used for the treatment of certain tumors by immuno-therapy, and myelopoietic factors, such as GCSF (Granulocyte Colony Stimulating Factor) or GMCSF (Granulocyte Monocyte Colony Stimulating Factor), which stimulate the growth and differentiation of blood cells and whereby blood which has been impoverished in blood cells as a result of chemotherapy can be enriched therewith.
One of the first cytokinins to be discovered was interleukin-1, to which a central activity in inflammation--chemotaxis of neutrophils--was initially attributed following experiments showing an activity of this type in vivo after injection (J. Oppenheim et al., 1986, Imm. Today, 7, 45-56). It is now known that interleukin-1 stimulates in vivo the expression of another cytokinin which is chemotactic towards neutrophils, namely interleukin-8 (originally called Neutrophil Chemotactic Factor, NCF). This cytokinin, whose amino acid sequence was determined in 1987 after isolation and purification and also by cloning and sequencing of its complementary DNA (K. Matsushima et al., 1988, J. Exp. Med., 1883-1893), is homologous with other cytokinins already known at the time of its discovery, namely the cytokinins produced by the .alpha. granules of platelets, such as PF4 (Platelet Factor 4) and PBP (Platelet Basic Protein). The family of known proteins homologous with interleukin-8, usually called the SIS family (representing Small Induced Secreted proteins), has grown considerably since 1987 [J. Oppenheim et al., 1991, Ann. Rev. Immun., 9, 617]. It currently includes the following cytokinins in particular: gro (also called MGSA: Melanoma Growth Stimulatory Activity) described by A. Anisowicz et al., 1987, Proc. Ntl. Acad. Sci. U.S.A., 84, 7188-7192, and A. Richmond et al., 1988, EMBO J., 7, 2025-2033, RANTES (Regulated upon Activation Normal T Expressed and presumably Secreted) described by T. Schall et al., 1988, J. Imm., 141, 1018-1025, MIP-1 (Macrophage Inflammatory Protein 1) described by S. D. Wolpe et al., 1988, J. Exp. Med., 167, 570-581, MIP-2 (Macrophage Inflammatory Protein 2) described by S. D. Wolpe et al., 1989, Proc. Ntl. Acad. Sci. U.S.A., 86, 612-616, and MCP-1 (Monocyte Chemoattractant Protein 1, also called MCAF: Monocyte Chemotactic and Activating Factor) described by Yoshimura et al., 1989, Proc. Ntl. Acad. Sci. U.S.A., 84, 9233-9237, and K. Matsushima et al., 1989, J. Expr. Med., 169, 1485-1489.
The cytokinin MCP-1, isolated from a line of gliomas by T. Yoshimura, op. cit., and from a line of monocytes by K. Matsushima et al., op. cit., exists in two forms with apparent molecular weights of 13 and 15 kDa, called MCP-1.alpha. and MCP-1.beta., which seem to correspond to post-translational modifications [Y. Jiang et al., 1990, J. Biol. Chem., 265, 1318-321]. The cytokinin MCP-1 has a chemotactic activity towards monocytes and basophils but not towards neutrophils (E. J. Leonard, 1990, Immunology Today, 11, 3, 97-101) and a stimulating e
REFERENCES:
Chang, H. C., et al. (1989) Int. Immunol. 1: 388-97.
Oppenheim, J. J., et al. (1991) Ann. Rev. Immunol. 9: 617-48.
Van Damme, J., et al. (1992) J. Exp. Med. 176: 59-65.
Ferrara et al. "Characterization of Recombinant Glycosylated Human Interleukin-2 Produced By A Recombinant Plasmid . . . ", FEBS Ltrs., 226(1): 47-52 (1987).
Singh et al. "Synergism Between Human Monocyte Chemotactic and Activating Factor and Bacterial . . . ", J. Immun., 151(5): 2786-2793 (1993).
Minty et al. "Molecular Cloning of the MCP-3 Chemokine Gene and Regulation of its Expression", Eur. Cytokine Netw., 4(2): 99-110 (1993).
Rollins et al. "Suppression of Tumor Formation in Vivo by Expression of the JE Gene in Malignant Cells", Mol. Cell. Biol., 11(6): 3125-3131 (1991).
Tepper et al. "Murine Interleukin-4 Displays Potent Anti-Tumor Activity In Vivo", Cell, 57: 503-512 (1989).
Caput Daniel
Ferrara Pascual
Miloux Brigitte
Minty Adrian
Vita Natalio
Fitzgerald David L.
Societe Anonyme: Elf Sanofi
LandOfFree
Chemokine NC28 (monocyte chemotactic protein-3, MCP-3) polypepti does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Chemokine NC28 (monocyte chemotactic protein-3, MCP-3) polypepti, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Chemokine NC28 (monocyte chemotactic protein-3, MCP-3) polypepti will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-862462