Thromb Haemost 2008; 99(05): 863-873
DOI: 10.1160/TH07-11-0703
Theme Issue Article
Schattauer GmbH

Haematopoietic growth factors and their therapeutic use

Meenu Wadhwa
1   Biotherapeutics Group, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, United Kingdom
,
Robin Thorpe
1   Biotherapeutics Group, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, United Kingdom
› Institutsangaben
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Publikationsverlauf

Received 27. November 2007

Accepted after minor revision 25. Januar 2008

Publikationsdatum:
30. November 2017 (online)

Summary

Haematopoietic growth factors constitute an important group of proteins that predominantly regulate the process of haematopoiesis. While some of these proteins have a very broad array of action on very early haematopoietic progenitors leading to multi-lineage increases in haematopoietic cell production and differentiation, others act in a restricted manner on specific committed terminally differentiated cell types. On the basis of their unique spectrum of activities, several factors are approved for clinical use in various indications while others are under investigation in the clinic either alone or as combination therapy. In this review, we have described factors which directly and in some cases indirectly influence haematopoiesis with particular focus on those factors which are either approved or show potential for clinical use. A brief description of the products that are currently available for clinical use is also provided. At present, several new products which include fusion proteins, peptide mimetics are either at the pre-clinical stage or in clinical development for various indications and these are also briefly described.

 
  • References

  • 1 Nicola NA. et al. Purification of a factor inducing differentiation in murine myelomonocytic leukemia cells. Identification as granulocyte colony-stimulating factor. J Biol Chem 1983; 258: 9017-9023.
  • 2 Welte K. et al. Purification and biochemical characterization of human pluripotent hematopoietic colony- stimulating factor. Proc Natl Acad Sci USA 1985; 82: 1526-1530.
  • 3 Nomura H. et al. Purification and characterization of human granulocyte colony-stimulating factor (G-CSF). EMBO J 1986; 5: 871-876.
  • 4 Nagata S. et al. Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. Nature 1986; 319: 415-418.
  • 5 Souza LM. et al. Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. Science 1986; 232: 61-65.
  • 6 Nicola NA. Hemopoietic cell growth factors and their receptors. Annu Rev Biochem 1989; 58: 45-77.
  • 7 Demetri GD, Griffin JD. Granulocyte colony-stimulating factor and its receptor. Blood 1991; 78: 2791-2808.
  • 8 Platzer E. Human hemopoietic growth factors. Eur J Haematol 1989; 42: 1-15.
  • 9 Ogawa M. Differentiation and proliferation of hematopoietic stem cells. Blood 1993; 81: 2844-2853.
  • 10 Rutella S. et al. Granulocyte colony-stimulating factor promotes the generation of regulatory DC through induction of IL-10 and IFN-alpha. Eur J Immunol 2004; 34: 1291-1302.
  • 11 Lieschke GJ, Burgess AW. Granulocyte colony-stimulating factor and granulocyte-macrophage colony- stimulating factor (1). N Engl J Med 1992; 327: 28-35.
  • 12 Lieschke GJ, Burgess AW. Granulocyte colony-stimulating factor and granulocyte-macrophage colony- stimulating factor (2). N Engl J Med 1992; 327: 99-106.
  • 13 Ozer H. et al. Update of recommendations for the use of hematopoietic colony-stimulating factors: evidence- based, clinical practice guidelines. American Society of Clinical Oncology Growth Factors Expert Panel. J Clin Oncol 2000; 18: 3558-3585.
  • 14 Roberts AW. G-CSF:. a key regulator of neutrophil production, but that’s not all! Growth Factors 2005; 23: 33-41.
  • 15 Heuser M. et al. Use of colony-stimulating factors for chemotherapy-associated neutropenia: review of current guidelines. Semin Hematol 2007; 44: 148-156.
  • 16 Ottmann OG. et al. Current status of growth factors in the treatment of acute myeloid and lymphoblastic leukemia. Semin Hematol 2007; 44: 183-192.
  • 17 Dührsen U. et al. Effects of recombinant human granulocyte colony-stimulating factor on hematopoietic progenitor cells in cancer patients. Blood 1988; 72: 2074-2081.
  • 18 Möhle R, Kanz L. Hematopoietic growth factors for hematopoietic stem cell mobilization and expansion. Semin Hematol 2007; 44: 193-202.
  • 19 Ings SJ. et al. Peripheral blood stem cell yield in 400 normal donors mobilised with granulocyte colony-stimulating factor (G-CSF): impact of age, sex, donor weight and type of G-CSF used. Br J Haematol 2006; 134: 517-525.
  • 20 Oh-eda M. et al. O-Linked sugar chain of human granulocyte stimulating factor protects it against polymerisation and denaturation allowing it to retain its biological activity. J Biol Chem 1990; 265: 11432-11435.
  • 21 Balaguer H. et al. Splenic rupture after granulocyte- colony-stimulating factor mobilization in a peripheral blood progenitor cell donor. Transfusion 2004; 44: 1260-1261.
  • 22 Tigue CC. et al. Granulocyte-colony stimulating factor administration to healthy individuals and persons with chronic neutropenia or cancer: an overview of safety considerations from the Research on Adverse Drug Events and Reports project. Bone Marrow Transplant 2007; 40: 185-192.
  • 23 Graber SE, Krantz SB. Erythropoietin and the control of red cell production. Annu Rev Med 1978; 29: 51-66.
  • 24 Lin FK. et al. Cloning and expression of the human erythropoietin gene. Proc Natl Acad Sci USA 1985; 82: 7580-7584.
  • 25 Constantinescu SN. et al. The erythropoietin receptor: Structure, activation and intracellular signal transduction. Trends Endocrinol Metab 1999; 10: 18-23.
  • 26 Takeuchi M. et al. Role of sugar chains in the in vitro biological activity of human erythropoietin produced in recombinant Chinese hamster ovary cells. J Biol Chem 1990; 265: 12127-12130.
  • 27 Lukowsky WA, Painter RH. Studies on the role of sialic acid in the physical and biological properties of erythropoietin. Can J Biochem 1972; 50: 909-917.
  • 28 Eschbach JW. et al. Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. Results of a combined phase I and II clinical trial. N Engl J Med 1987; 316: 73-78.
  • 29 de Campos E. et al. Clinical and in vitro effects of recombinant human erythropoietin in patients receiving intensive chemotherapy for small-cell lung cancer. J Clin Oncol 1995; 13: 1623-1631.
  • 30 Osterborg A. et al. Recombinant human erythropoietin in transfusion-dependent anemic patients with multiple myeloma and non-Hodgkin’s lymphoma–a randomized multicenter study. The European Study Group of Erythropoietin (Epoetin Beta) Treatment in Multiple Myeloma and Non-Hodgkin’s Lymphoma. Blood 1996; 87: 2675-2682.
  • 31 Means RT. Jr et al. Treatment of the anemia of rheumatoid arthritis with recombinant human erythropoietin: clinical and in vitro studies. Arthritis Rheum 1989; 32: 638-642.
  • 32 Egrie JC, Browne JK. Development and characterization of novel erythropoiesis stimulating protein (NESP). Br J Cancer 2001; 84 (Suppl. 01) 3-10.
  • 33 Elliott S. et al. Enhancement of therapeutic protein in vivo activities through glycoengineering. Nat Biotechnol 2003; 21: 414-421.
  • 34 Casadevall N. et al. Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin. N Engl J Med 2002; 346: 469-475.
  • 35 Metcalf D. et al. Biologic properties in vitro of a recombinant human granulocyte-macrophage colony-stimulating factor. Blood 1986; 67: 37-45.
  • 36 Ruef C, Coleman DL. Granulocyte-macrophage colony-stimulating factor: pleiotropic cytokine with potential clinical usefulness. Rev Infect Dis 1990; 12: 41-62.
  • 37 Jones TC. The effect of granulocyte-macrophage colony stimulating factor (rGM-CSF) on macrophage function in microbial disease. Med Oncol 1996; 13: 141-147.
  • 38 Caux C. et al. GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells. Nature 1992; 360: 258-261.
  • 39 Wong GG. et al. Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant proteins. Science 1985; 228: 810-815.
  • 40 Lee F. et al. Isolation of cDNA for a human granulocyte- macrophage colony-stimulating factor by functional expression in mammalian cells. Proc Natl Acad Sci USA 1985; 82: 4360-4364.
  • 41 Gearing DP. et al. Expression cloning of a receptor for human granulocyte-macrophage colony-stimulating factor. EMBO J 1989; 8: 3667-3676.
  • 42 Hayashida K. et al. Molecular cloning of a second subunit of the receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF): reconstitution of a high-affinity GM-CSF receptor. Proc Natl Acad Sci USA 1990; 87: 9655-9659.
  • 43 Gerhartz HH. et al. Randomized, double-blind, placebo-controlled, phase III study of recombinant human granulocyte-macrophage colony-stimulating factor as adjunct to induction treatment of high-grade malignant non-Hodgkin’s lymphomas. Blood 1993; 82: 2329-2339.
  • 44 Mellstedt H. et al. Augmentation of the immune response with granulocyte-macrophage colony-stimulating factor and other hematopoietic growth factors. Curr Opin Hematol 1999; 6: 169-175.
  • 45 Lieschke GJ. et al. Effects of bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor in patients with advanced malignancy. Ann Intern Med 1989; 110: 357-364.
  • 46 Wadhwa M. et al. Production of neutralizing granulocyte- macrophage colony-stimulating factor (GMCSF) antibodies in carcinoma patients following GMCSF combination therapy. Clin Exp Immunol 1996; 104: 351-358.
  • 47 Wadhwa M. et al. Immunogenicity of granulocytemacrophage colony-stimulating factor (GM-CSF) products in patients undergoing combination therapy with GM-CSF. Clin Cancer Res 1999; 5: 1353-1361.
  • 48 Huang E. et al. The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus. Cell 1990; 63: 225-233.
  • 49 Williams DE. et al. Identification of a ligand for the c-kit proto-oncogene. Cell 1990; 63: 167-174.
  • 50 Zsebo KM. et al. Identification, purification, and biological characterization of hematopoietic stem cell factor from buffalo rat liver–conditioned medium. Cell 1990; 63: 195-201.
  • 51 Huang EJ. et al. Differential expression and processing of two cell associated forms of the kit-ligand: KL-1 and KL-2. Mol Biol Cell 1992; 3: 349-362.
  • 52 Arakawa T. et al. Glycosylated and unglycosylated recombinant-derived human stem cell factors are dimeric and have extensive regular secondary structure. J Biol Chem 1991; 266: 18942-18948.
  • 53 Broudy VC. Stem cell factor and hematopoiesis. Blood 1997; 90: 1345-1364.
  • 54 Glaspy JA. et al. Peripheral blood progenitor cell mobilization using stem cell factor in combination with filgrastim in breast cancer patients. Blood 1997; 9: 2939-2951.
  • 55 To LB. et al. Successful mobilization of peripheral blood stem cells after addition of ancestim (stem cell factor) in patients who had failed a prior mobilization with filgrastim (granulocyte colony-stimulating factor) alone or with chemotherapy plus filgrastim. Bone Marrow Transplant 2003; 31: 371-378.
  • 56 Jensen BM. et al. Targeting kit activation: a potential therapeutic approach in the treatment of allergic inflammation. Inflamm Allergy Drug Targets 2007; 6: 57-62.
  • 57 Paul SR. et al. Molecular cloning of a cDNA encoding interleukin 11, a stromal cell-derived lymphopoietic and hematopoietic cytokine. Proc Natl Acad Sci USA 1990; 87: 7512-7516.
  • 58 Turner KJ, Clark SC. Interleukin-11; biological and clinical perspectives. Hematopoietic growth factors in clinical applications.. Marcel Dekker; 1995: 315-336.
  • 59 Du XX, Williams DA. Interleukin-11: a multifunctional growth factor derived from the hematopoietic microenvironment. Blood 1994; 83: 2023-2030.
  • 60 Paul SR, Schendel P. The cloning and biological characterization of recombinant human interleukin 11. Int J Cell Cloning 1992; 10: 135-143.
  • 61 Quesniaux VF. et al. Interleukin-11 stimulates multiple phases of erythropoiesis in vitro. Blood 1992; 80: 1218-1223.
  • 62 Gordon MS. et al. A phase I trial of recombinant human interleukin-11 (neumega rhIL-11 growth factor) in women with breast cancer receiving chemotherapy. Blood 1996; 87: 3615-3624.
  • 63 Kaye JA. FDA licensure of NEUMEGA to prevent severe chemotherapy-induced thrombocytopenia. Stem Cells 1998; 16 (Suppl. 02) 207-223.
  • 64 Kaushansky K. Thrombopoietin. N Engl J Med 1998; 339: 746-754.
  • 65 de Sauvage FJ. et al. Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand. Nature 1994; 369: 533-538.
  • 66 Kaushansky K. et al. Promotion of megakaryocyte progenitor expansion and differentiation by the c-Mpl ligand thrombopoietin. Nature 1994; 369: 568-571.
  • 67 Lok S. et al. Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo. Nature 1994; 369: 565-58.
  • 68 Broudy VC. et al. Human platelets display high-affinity receptors for thrombopoietin. Blood 1997; 89: 1896-1904.
  • 69 Fielder PJ. et al. Human platelets as a model for the binding and degradation of thrombopoietin. Blood 1997; 89: 2782-2788.
  • 70 Deutsch VR, Tomer A. Megakaryocyte development and platelet production. Br J Haematol 2006; 134: 453-466.
  • 71 Kaushansky K. Lineage-specific hematopoietic growth factors. N Engl J Med 2006; 354: 2034-2045.
  • 72 Yang M. et al. Expression of interleukin (IL) 1 type I and type II receptors in megakaryocytic cells and enhancing effects of IL-1beta on megakaryocytopoiesis and NF-E2 expression. Br J Haematol 2000; 111: 371-380.
  • 73 Kaushansky K. Thrombopoietin and the hematopoietic stem cell. Ann NY Acad Sci 2005; 1044: 139-141.
  • 74 Ivanovic Z. et al. A clinical-scale expansion of mobilized CD 34+ hematopoietic stem and progenitor cells by use of a new serum-free medium. Transfusion 2006; 46: 126-131.
  • 75 Begley CG, Basser RL. Biologic and structural differences of thrombopoietic growth factors. Semin Hematol 2000; 37: 19-27.
  • 76 Kuter DJ. New thrombopoietic growth factors. Blood 2007; 109: 4607-4616.
  • 77 Vadhan-Raj S. et al. Stimulation of megakaryocyte and platelet production by a single dose of recombinant human thrombopoietin in patients with cancer. Ann Intern Med 1997; 126: 673-681.
  • 78 Li J. et al. Thrombocytopenia caused by the development of antibodies to thrombopoietin. Blood 2001; 98: 3241-3248.
  • 79 Basser RL. et al. Development of pancytopenia with neutralizing antibodies to thrombopoietin after multicycle chemotherapy supported by megakaryocyte growth and development factor. Blood 2002; 99: 2599-2602.
  • 80 Ciurea SO, Hoffman R. Cytokines for the treatment of thrombocytopenia. Semin Hematol 2007; 44: 166-182.
  • 81 Bussel JB. et al. AMG 531, a thrombopoiesisstimulating protein, for chronic ITP. N Engl J Med 2006; 355: 1672-1681.
  • 82 Bussel JB. et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med 2007; 357: 2237-2247.
  • 83 Jenkins JM. et al. Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist. Blood 2007; 109: 4739-4741.
  • 84 Stasi R. et al. Idiopathic thrombocytopenic purpura: Current concepts in pathophysiology and management. Thromb Haemost 2008; 99: 4-13.
  • 85 Clark SC, Kamen R. The human hematopoietic colony- stimulating factors. Science 1987; 236: 1229-1237.
  • 86 Metcalf D. Control of granulocytes and macrophages: molecular, cellular, and clinical aspects. Science 1991; 254: 529-533.
  • 87 Clark-Lewis I. et al. Purification to apparent homogeneity of a factor stimulating the growth of multiple lineages of hemopoietic cells. J Biol Chem 1984; 259: 7488-7494.
  • 88 Yang YC. et al. Human IL-3 (multi-CSF): identification by expression cloning of a novel hematopoietic growth factor related to murine IL-3. Cell 1986; 47: 3-10.
  • 89 Leary AG. et al. Recombinant gibbon interleukin 3 supports formation of human multilineage colonies and blast cell colonies in culture: comparison with recombinant human granulocyte-macrophage colony-stimulating factor. Blood 1987; 70: 1343-1348.
  • 90 Kitamura T. et al. Expression cloning of the human IL-3 receptor cDNA reveals a shared beta subunit for the human IL-3 and GM-CSF receptors. Cell 1991; 66: 1165-1174.
  • 91 Miyajima A. et al. Receptors for granulocyte-macrophage colony-stimulating factor, interleukin-3, and interleukin-5. Blood 1993; 82: 1960-1974.
  • 92 Platzer E. et al. Biological activities of a human pluripotent hemopoietic colony stimulating factor on normal and leukemic cells. J Exp Med 1985; 162: 1788-1801.
  • 93 Eder M. et al. IL-3 in the clinic. Stem Cells 1997; 15: 327-333.
  • 94 Ganser A. et al. Effects of recombinant human interleukin- 3 in patients with myelodysplastic syndromes. Blood 1990; 76: 455-462.
  • 95 Ganser A. et al. Effects of recombinant human interleukin- 3 in patients with normal hematopoiesis and in patients with bone marrow failure. Blood 1990; 76: 666-676.
  • 96 Kurzrock R. Thrombopoietic factors in chronic bone marrow failure states: the platelet problem revisited. Clin Cancer Res 2005; 11: 1361-1367.
  • 97 Tushinski RJ. et al. Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy. Cell 1982; 28: 71-81.
  • 98 Stanley ER. et al. CSF-1–a mononuclear phagocyte lineage-specific hemopoietic growth factor. J Cell Biochem 1983; 21: 151-159.
  • 99 Ralph P, Sampson-Johannes A. Macrophage growth and stimulating factor, M-CSF. Prog Clin Biol Res 1990; 338: 43-63.
  • 100 Kirma N. et al. Elevated expression of the oncogene c-fms and its ligand, the macrophage colony-stimulating factor-1, in cervical cancer and the role of transforming growth factor-beta 1 in inducing c-fms expression. Cancer Res 2007; 67: 1918-1926.
  • 101 Sherr CJ. Colony-stimulating factor-1 receptor. Blood 1990; 75: 1-12.
  • 102 Chitu V, Stanley ER. Colony-stimulating factor-1 in immunity and inflammation. Curr Opin Immunol 2006; 18: 39-48.
  • 103 Dinarello CA. Interleukin-1 and interleukin-1 antagonism. Blood 1991; 77: 1627-1652.
  • 104 Oppenheim JJ, Gery I. Interleukin 1 is more than an interleukin. Immunol Today 1982; 3: 113-119.
  • 105 Bagby GC. Jr. Interleukin-1 and hematopoiesis. Blood Rev 1989; 3: 152-161.
  • 106 Smith KA. T-cell growth factor. Immunol Rev 1980; 51: 337-357.
  • 107 Gearing A. et al. Human B cell proliferation is stimulated by interleukin 2. Immunol Lett 1985; 9: 105-108.
  • 108 Robb R. Interleukin-2: the molecule and its function. Immunol Today 1984; 5: 203-209.
  • 109 Trinchieri G. et al. Response of resting human peripheral blood natural killer cells to interleukin 2. J Exp Med 1984; 160: 1147-1169.
  • 110 Callard RE. Immunoregulation by interleukin-4 in man. Br J Haematol 1991; 78: 293-299.
  • 111 Yokota T. et al. Molecular biology of interleukin 4 and interleukin 5 genes and biology of their products that stimulate B cells, T cells and hemopoietic cells. Immunol Rev 1988; 102: 137-187.
  • 112 Kishimoto T. The biology of interleukin-6. Blood 1989; 74: 1-10.
  • 113 Rennick D. et al. Interleukin-6 interacts with interleukin- 4 and other hematopoietic growth factors to selectively enhance the growth of megakaryocytic, erythroid, myeloid, and multipotential progenitor cells. Blood 1989; 73: 1828-1835.
  • 114 Clutterbuck E. et al. Recombinant human interleukin 5 is an eosinophil differentiation factor but has no activity in standard human B cell growth factor assays. Eur J Immunol 1987; 17: 1743-1750.
  • 115 Clutterbuck EJ. et al. Human interleukin-5 (IL-5) regulates the production of eosinophils in human bone marrow cultures: comparison and interaction with IL-1, IL-3, IL-6, and GMCSF. Blood 1989; 73: 1504-1512.
  • 116 Namen AE. et al. B cell precursor growth-promoting activity. Purification and characterization of a growth factor active on lymphocyte precursors. J Exp Med 1988; 167: 988-1002.
  • 117 Conlon PJ. et al. Murine thymocytes proliferate in direct response to interleukin-7. Blood 1989; 74: 1368-1373.
  • 118 Yang YC. et al. Expression cloning of cDNA encoding a novel human hematopoietic growth factor: human homologue of murine T-cell growth factor P40. Blood 1989; 74: 1880-1884.
  • 119 Kobayashi M. et al. Identification and purification of natural killer cell stimulatory factor (NKSF),a cytokine with multiple biologic effects on human lymphocytes. J Exp Med 1989; 170: 827-845.
  • 120 Lieberman MD. et al. Natural killer cell stimulatory factor (NKSF) augments natural killer cell and antibody-dependent tumoricidal response against colon carcinoma cell lines. J Surg Res 1991; 50: 410-415.
  • 121 Carson WE. et al. Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor. J Exp Med 1994; 180: 1395-1403.
  • 122 Grabstein KH. et al. Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor. Science 1994; 264: 965-968.
  • 123 Goey H. et al. Inhibition of early murine hemopoietic progenitor cell proliferation after in vivo locoregional administration of transforming growth factor-beta 1. J Immunol 1989; 143: 877-880.
  • 124 Rigby WF. et al. The effects of recombinant-DNAderived interferons on the growth of myeloid progenitor cells. Blood 1985; 65: 858-861.
  • 125 Naranda T. et al. Activation of erythropoietin receptor through a novel extracellular binding site. Endocrinology 2002; 143: 2293-2302.
  • 126 Thorpe R, Wadhwa M. Protein therapeutics and their immunogenicity. Eur J Hosp Pharm Pract 2006; 12: 17-18.
  • 127 Wadhwa M, Thorpe R. Unwanted immunogenicity: Is it a problem for biosimilar products?. BIOforum Europe 2006; 10: 46-48.
  • 128 Wadhwa M, Thorpe R. Unwanted immunogenicity: Implications for follow-on biologicals. Drug Inf J 2007; 41: 1-10.
  • 129 Mellstedt H. et al. The challenge of biosimilars. Ann Oncol 2007 Epub ahead of print.