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Advances and challenges in developing cytokine fusion proteins as improved therapeutics

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Pages 181-194 | Published online: 02 Feb 2009

Bibliography

  • Dranoff G. Cytokines in cancer pathogenesis and cancer therapy. Nat Rev Cancer 2004;4:11-22
  • Marshall E. Cancer trial of interleukin-12 halted. Science 1995;268:1555
  • Leonard JP, Sherman ML, Fisher GL, et al. Effects of single dose interleukin-12 exposure on interleukin-12 associated toxicity and interferon-γ production. Blood 1997;90:2541-8
  • Forni G, Giovarelli M, Santoni A. Lymphokine-activated tumor inhibition in vivo: 1. The local administration of interleukin 2 triggers nonreactive lymphocytes from tumor-bearing mice to inhibit tumor growth. J Immunol 1985;134:1305-11
  • Chang CH, Rossi EA, Goldenberg DM. The dock and lock method: a novel platform technology for building multivalent, multifunctional structures of defined composition with retained bioactivity. Clin Cancer Res 2007;13(19 Suppl):5586s-91s
  • Yeh P, Landais D, Lemaitre M, et al. Design of yeast-secreted albumin derivatives for human therapy: biological and antiviral properties of a serum albumin-CD4 genetic conjugate. Proc Natl Acad Sci USA 1992;89:1904-8
  • Poznansky MJ, Halford J, Taylor D. Growth hormone-albumin conjugates. Reduced renal toxicity and altered plasma clearance. FEBS Lett 1988;239:18-22
  • Makrides SC, Nygren PA, Andrews B, et al. Extended in vivo half-life of human soluble complement receptor type 1 fused to a serum albumin binding receptor. J Pharmacol Exp Ther 1996;277:534-42
  • Kurtzhals P, Havelund S, Jonassen I, et al. Albumin binding of insulins acylated with fatty acids: characterization of the ligand-protein interaction and correlation between binding affinity and timing of the insulin effect in vivo. Biochem J 1995;312:725-31
  • Dennis MS, Zhang M, Meng G, et al. Albumin binding as a general strategy for improving the pharmacokinetics of proteins. J Biol Chem 2002;277:35035-43
  • Chaudhury C, Mehnaz S, Robinson JM, et al. The major histocompatibility complex-related Fc receptor for IgG (FcRn) binds albumin and prolongs its lifespan. J Exp Med 2003;197:315-22
  • Chaudhury C, Brooks CL, Carter DC, et al. Albumin binding to FcRn: distinct from the FcRn-IgG interaction. Biochemistry 2006;45:4983-90
  • Halpern W, Riccobene TA, Agostini H, et al. Albugranin, a recombinant human granulocyte colony stimulating factor (G-CSF) genetically fused to recombinant human albumin induces prolonged myelopoietic effects in mice and monkeys. Pharm Res 2002;19:1720-9
  • Osborn BL, Sekut L, Corcoran M, et al. Albutropin: a growth hormone-albumin fusion with improved pharmacokinetics and pharmacodynamics in rats and monkeys. Eur J Pharmacol 2002;456:149-58
  • Sung C, Nardelli B, LaFleur DW, et al. An IFN-beta-albumin fusion protein that displays improved pharmacokinetic and pharmacodynamic properties in nonhuman primates. J Interferon Cytokine Res 2003;23:25-36
  • Yao Z, Dai W, Perry J, et al. Effect of albumin fusion on the biodistribution of interleukin-2. Cancer Immuno Immunother 2004;53:404-10
  • Osborn BL, Olsen HS, Nardelli B, et al. Pharmacokinetic and pharmacodynamic studies of a human serum albumin-interferon-α fusion protein in cynomolgus monkeys. J Pharmacol Exp Ther 2002;303:540-8
  • Duttaroy A, Kanakaraj P, Osborn BL, et al. Development of a long-acting insulin analog using albumin fusion technology. Diabetes 2005;54:251-8
  • Syed S, Schuyler PD, Kulczycky M, Sheffiled WP. Potent antithrombin activity and delayed clearance from the circulation characterize recombinant hirudin genetically fused to albumin. Blood 1997;89:3243-52
  • Weimer T, Wormsbacher W, Kronthaler U, et al. Prolonged in-vivo half-life of factor VIIa by fusion to albumin. Thromb Haemost 2008;99:659-67
  • Dou WF, Lei JY, Zhang LF, et al. Expression, purification, and characterization of recombinant human serum albumin fusion protein with two human glucagon-like peptide-1 mutants in Pichia pastoris. Protein Expr Purif 2008;61:45-9
  • Huang YJ, Lundy PM, Lazaris A, et al. Substantially improved pharmacokinetics of recombinant human butyrylcholinesterase by fusion to human serum albumin. BMC Biotechnol 2008;8:50
  • Wang W, Qu Y, Shi Y. AlbuBNP, a recombinant B-type natriuretic peptide and human serum albumin fusion hormone, as long-term therapy of congestive heart failure. Pharm Res 2004;21:2105-11
  • Muller D, Karle A, Meibburger B, et al. Improved pharmacokinetics of recombinant bispecific antibody molecules by fusion to human serum albumin. J Biol Chem 2007;282:12650-60
  • Subramanian GM, Fiscella M, Lamouse A, et al. Albinterferon a-2b: a genetic fusion protein for the treatment of chronic hepatitis C. Nat Biotechnol 2007;25:1411-9
  • Ponka P, Lok CN. The transferrin receptor: role in health and disease. Int J Biochem Cell Biol 1999;31:1111-37
  • Daniels TR, Delgado T, Rodriguez JA, et al. The transferrin receptor part I: biology and targeting with cytotoxic antibodies for the treatment of cancer. Clin Immunol 2006;121:144-58
  • Daniels TR, Delgado T, Helguera G, Penichet ML. The transferrin receptor part II: targeted delivery of therapeutic agents into cancer cells. Clin Immunol 2006;121:159-76
  • Qian ZM, Li H, Sun H, Ho K. Targeted delivery via the transferrin receptor-mediated endocytosis pathway. Pharmacol Rev 2002;54:561-87
  • Zari PR, Feeney R. Resistance of metal complexes of conalbumin and transferrin to proteolysis and to thermal denaturation. J Biol Chem 1958;232:293-302
  • Banerjee D, Flanagan PR, Cluett J, et al. Transferrin receptors in the human gastrointestinal tract. Relationship to body iron stores. Gastroenterology 1986;91:861-9
  • Bai Y, Ann DK, Shen WC. Recombinant granulocyte colony-stimulating factor-transferrin fusion protein as an oral myelopoietic agent. Proc Natl Acad Sci USA 2005;102:7272-6
  • Zak O, Trinder D, Aisen P. Primary receptor-recognition site of human transferrin is in the C-terminal lobe. J Biol Chem 1994;269:7110-4
  • Bai Y, Shen WC. Improving the oral efficacy of recombinant granulocyte colony-stimulating factor and transferrin fusion protein by spacer optimization. Pharm Res 2006;23:2116-21
  • Shin SU, Friden P, Moran M, et al. Transferrin-antibody fusion proteins are effective in brain targeting. Proc Natl Acad Sci USA 1995;92:2820-4
  • Park E, Starzyk RM, McGrath JP, et al. Production and characterization of fusion proteins containing transferrin and nerve growth factor. J Drug Target 1998;6:53-64
  • Lo KM, Sudo Y, Chen J, et al. High level expression and secretion of Fc-X fusion proteins in mammalian cells. Protein Eng 1998;11:495-500
  • O'reilly MS, Boehm T, Shing Y, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 1997;88:277-85
  • Folkman J. Antiangiogenesis in cancer therapy-endostatin and its mechanisms of action. Exp Cell Res 2006;312:594-607
  • Thomas JP, Arzoomanian RZ, Alberti D, et al. Phase I pharmacokinetic and pharmacodynamic study of recombinant human endostatin in patients with advanced solid tumors. J Clin Oncol 2003;21:223-31
  • Sim BK. Angiostatin and endostatin: endothelial cell-specific endogenous inhibitors of angiogenesis and tumor growth. Angiogenesis 1998;2:37-48
  • Tjin Tham Sjin RM, Satchi-Fainaro R, Birsner AE, et al. A 27-amino-acid synthetic peptide corresponding to the NH2-terminal zinc-binding domain of endostatin is responsible for its antitumor activity. Cancer Res 2005;65:3656-63
  • Lee TY, Tjin Tham Sjin RM, Movahedi S, et al. Linking antibody Fc domain to endostatin significantly improves endostatin half-life and efficacy. Clin Cancer Res 2008;14:1487-93
  • Celik I, Surucu O, Dietz C, et al. Therapeutic efficacy of endostatin exhibits a biphasic dose-response curve. Cancer Res 2005;65:11044-50
  • Glaspy J, Bukowski R, Steinberg D, et al. Impact of therapy with epoetin alfa on clinical outcomes in patients with nonmyeloid malignancies during cancer chemotherapy in community oncology practice. J Clin Oncol 1997;15:1218-34
  • Littlewood TJ, Bajetta E, Nortier JW, et al. Effects of epoetin alfa on hematologic parameters and quality of life in cancer patients receiving nonplatinum chemotherapy: results of a randomized, double-blind, placebo-controlled trial. J Clin Oncol 2001;19:2865-74
  • Egrie JC, Browne JK. Development and characterization of novel erythropoiesis stimulating protein (NESP). Nephrol Dial Transplant 2001;16:3-13
  • Way JC, Lauder S, Brunkhorst B, et al. Improvement of Fc-erythropoietin structure and pharmacokinetics by modification at a disulfide bond. Protein Eng Des Sel 2005;18:111-8
  • Bitonti AJ, Dumont JA, Low SC, et al. Pulmonary delivery of an erythropoietin Fc fusion protein in non-human primates through an immunoglobulin transport pathway. Proc Natl Acad Sci USA 2004;101:9763-8
  • Ortiz-Sánchez E, Helguera G, Daniels TR, et al. Antibody-cytokine fusion proteins: applications in cancer therapy. Expert Opin Biol Ther 2008;8:609-32
  • Shin SO, Morrison SL. Expression and characterization of an antibody binding specificity joined to insulin-like growth factor 1: potential applications for cellular targeting. Proc Natl Acad Sci USA 1990;87:5322-6
  • Gillies SD, Wesolowski JS, Lo KM. Targeting human cytotoxic T lymphocytes to kill heterologous epidermal growth factor receptor-bearing tumor cells. J Immunol 1991;146:1067-71
  • Shin SO, Friden P, Moran M, Morrison SL. Functional properties of antibody insulin-like growth factor fusion proteins. J Biol Chem 1994;269:4979-85
  • Camemolla B, Borsi L, Blza E, et al. Enhancement of the antitumor properties of interleukin-2 by its targeted delivery to the tumor blood vessel extracellular matrix. Blood 2002;99:1659-65
  • Wagner K, Schulz P, Scholz A, et al. The targeted immunocytokine L19-IL2 efficiently inhibits the growth of orthotopic pancreatic cancer. Clin Cancer Res 2008;14:4951-60
  • Gillies SD, Lan Y, Williams S, et al. An Anti-CD20-IL2 immunocytokine is highly efficacious in a SCID mouse model of established human B lymphoma. Blood 2005;105:3972-8
  • Neal ZC, Yang JC, Rakhmilevich AL, et al. Enhanced activity of hu14.18-IL2 immunocytokine against murine NXS2 neuroblastoma when combined with interleukin 2 therapy. Clin Cancer Res 2004;10:4839-47
  • Lode HN, Xiang R, Varki NM, et al. Targeted interleukin-2 therapy for spontaneous neuroblastoma metastases to bone marrow. J Natl Cancer Inst 1997;89:1586-94
  • Gillies SD, Young D, Lo KM, Roberts S. Biological activity and in vivo clearance of antitumor antibody/cytokine fusion proteins. Bioconj Chem 1993;4:230-5
  • Gillies SD, Reilly EB, Lo KM, Reisfeld RA. Antibody-targeted interleukin 2 stimulates T-cell killing of autologous tumor cells. Proc Nat Acad Sci USA 1992;89:1428-32
  • Hu P, Mizokami M, Ruoff G, et al. Generation of low-toxicity interleukin-2 fusion proteins devoid of vasopermeability activity. Blood 2003;101:4853-61
  • Dolman CS, Mueller BM, Lode HN, et al. Suppression of human prostate carcinoma metastases in severe combined immunodeficiency mice by interleukin 2 immunocytokine therapy. Clin Cancer Res 1998;4:2552-7
  • Xiang R, Lode HN, Dolman CS, et al. Elimination of established murine colon carcinoma metastases by antibody-interleukin 2 fusion protein therapy. Cancer Res 1997;57:4948-55
  • Gillies SD, Lan Y, Lo KM. Improving the efficacy of antibody-interleukin 2 fusion proteins by reducing their interaction with Fc receptors. Cancer Res 1999;59:2159-66
  • Xu X, Clarke P, Szalai G, et al. Targeting and therapy of carcinoembryonic antigen-expressing tumors in transgenic mice with an antibody-interleukin 2 fusion protein. Cancer Res 2000;60:4475-84
  • Hornick JL, Khawli LA, Hu P, et al. Chimeric CLL-1 antibody fusion proteins containing granulocyte-macrophage colony-stimulating factor or interleukin-2 with specificity for B-cell malignancies exhibit enhanced effector functions while retaining tumor targeting properties. Blood 1997;89:4437-47
  • Christ O, Seiter S, Matzku S, et al. Efficacy of local versus systematic applications of antibody-cytokine fusion proteins in tumor therapy. Clin Cancer Res 2001;7:985-98
  • Penichet ML, Dela Cruz JS, Shin SU, Morrison SL. A recombinant IgG3-(IL-2) fusion protein for the treatment of human HER2/neu expressing tumors. Hum Antibodies 2001;10:43-9
  • Lo KM, Lan Y, Lander S, et al. huBC1-IL12, an immunocytokine which targets EDB-containing oncofecal fibronectin in tumors and tumor vasculature, shows potent anti-tumor activity in human tumor models. Cancer Immunol Immunother 2007;56:447-57
  • Gafner V, Trachsel E, Neri D. An engineered antibody-interleukin-12 fusion protein with enhanced tumor vascular targeting properties. Int J Cancer 2006;19:2205-12
  • Halin C, Gafner V, Villani ME, et al. Synergistic therapeutic effects of a tumor targeting antibody fragment, fused to interleukin 12 and to tumor necrosis factor α. Cancer Res 2003;63:3202-10
  • Halin C, Rondini S, Nilsson F, et al. Enhancement of the antitumor activity of interleukin-12 by targeted delivery to neovasculature. Nat Biotechnol 2002;20:264-9
  • Heuser C, Diehl V, Abken H, Hombach A. Anti-CD30-IL-12 antibody-cytokine fusion protein that induces IFN-γ secretion of T cells and NK cell-mediated lysis of Hodgkin's lymphoma-derived tumor cells. Int J Cancer 2003;106:545-52
  • Peng LS, Penichet ML, Morrison SL. A single-chain IL-12 IgG3 antibody fusion protein retains antibody specificity and IL-12 bioactivity and demonstrates antitumor activity. J Immunol 1999;163:250-8
  • Gillies SD, Lan Y, Wesolowski JS, et al. Antibody-IL-12 fusion proteins are effective in SCID mouse models of prostate and colon carcinoma metastases. J Immunol 1998;160:6195-6203
  • Kaspar M, Trachsel E, Neri D. The antibody-mediated targeted delivery of interleukin-15 and GM-CSF to the tumor neovasculature inhibits tumor growth and metastasis. Cancer Res 2007;67:4940-8
  • Batova A, Kamps A, Gillies SD, et al. The ch14.18-GM-CSF fusion protein is effective at mediating antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity in vitro. Clin Cancer Res 1999;5:4259-63
  • Metelitsa LS, Gillies SD, Super M, et al. Antidisialoganglioside/granulocyte macrophage-colony-stimulating factor fusion protein facilitates neutrophil antibody-dependent cellular cytotoxicity and depends on FcγRII (CD32) and Mac-1 (CD11b/CD18) for enhanced effector cell adhesion and azuophil granule exocytosis. Blood 2002;99:4166-73
  • Dela Cruz JS, Trinh KR, Morrison SL, Penichet ML. Recombinant anti-human HER2/neu IgG3-(GM-CSF) fusion protein retains antigen specificity and cytokine function and demonstrates antitumor activity. J Immunol 2000;165:5112-21
  • Gillies SD, Young D, Lo KM, Reisfeld R. Expression of genetically engineered immunoconjugates of lymphotoxin and a chimeric anti-ganglioside GD2 antibody. Hybridoma 1991;10:347-56
  • Cho HM, Rosenblatt JD, Kang YS, et al. Enhanced inhibition of murine tumor and human breast tumor xenografts using targeted delivery of an antibody-endostatin fusion protein. Mol Cancer Ther 2005;4:956-67
  • Huang TH, Chintalacharuvu KR, Morrison SL. Targeting IFN-α to B cell lymphoma by a tumor-specific antibody elicits potent antitumor activities. J Immunol 2007;179:6881-8
  • Chang CH, Rossi E, Loo M, et al. A modular method to prepare novel tetrameric cytokines, IFN, G-CSF, and EPO, with improved pharmacokinetics by the Dock-and-Lock (DNL) platform technology [abstract 4906]. Proc Am Assoc Cancer Res 2008;49:1168
  • Gillies SD, Lan Y, Brunkhorst B, et al. Bi-functional cytokine fusion proteins for gene therapy and antibody-targeted treatment of cancer. Cancer Immunol Immunother 2002;51:449-60
  • Helguera G, Rodriguez JA, Penichet ML. Cytokines fused to antibodies and their combinations as therapeutic agents against different peritoneal HER2/neu expressing tumors. Mol Cancer Ther 2006;5:1029-40
  • Schanzer JM, Baeuerle PA, Dreier T, Kufer P. A human cytokine/single-chain antibody fusion protein for simultaneous delivery of GM-CSF and IL-2 to Ep-CAM overexpressing tumor cells. Cancer Immun 2006;6:4-14
  • Schanzer JM, Fichtner I, Baeuerle PA, Kufer P. Antitumor activity of a dual cytokine/single-chain antibody fusion protein for simultaneous delivery of GM-CSF and IL-2 to Ep-CAM expressing tumor cells. I Immunother 2006;29:477-88
  • Harvill ET, Morrison SL. An IgG3-IL2 fusion protein activates complement, binds Fc gamma RI, generates LAK activity and shows enhanced binding to the high affinity IL-2R. Immunotechnology 1995;1:95-105
  • Harvill ET, Morrison SL. An IgG3-IL-2 fusion protein has higher affinity than hrIL-2 for the IL-2R alpha subunit: real time measurement of ligand binding. Mol Immunol 1996;33:1007-14
  • Harvill ET, Fleming JM, Morrison SL. In vivo properties of an IgG3-IL-2 fusion protein: a general strategy for immune potentiation. J Immunol 1996;157:3165-70
  • Penichet ML, Harvill ET, Morrison SL. An IgG3-IL-2 fusion protein recognizing a murine B cell lymphoma exhibits effective tumor imaging and antitumor activity. J Interferon Cytokine Res 1998;18:597-607
  • Gillies SD, Lo KM, Burger C, et al. Improved circulating half-life and efficacy of an antibody-interleukin 2 immunocytokine based on reduced intracellular proteolysis. Clin Cancer Res 2002;8:210-6
  • Ko YJ, Bubley GJ, Weber R, et al. Safety, pharmacokinetics, and biological pharmacodynamics of the immunocytokine EMD 273066 (huKS-IL2): results of a phase I trial in patients with prostate cancer. J Immunother 2004;27:232-9
  • King DM, Albertini MR, Schalch H, et al. Phase I clinical trial of the immunocytokine EMD 273063 in melanoma patients. J Clin Oncol 2004;22:4463-73
  • Osenga KL, Hank JA, Albertini MR, et al. A phase I clinical trial of the hu14.18-IL2 (EMD 273063) as a treatment for children with refractory or recurrent neuroblastoma and melanoma: a study of the children's oncology group. Clin Cancer Res 2006;12:1750-9
  • Shusterman S, London WB, Gillies SD, et al. Anti-neuroblastoma activity of hu14.18-IL2 against minimal residual disease in a Children's Oncology Group (COG) phase II study [abstract 3002]. J Clin Oncol 2008;26(Suppl)
  • Newlon MG, Roy M, Morikis D, et al. The molecular basis for protein kinase A anchoring revealed by solution NMR. Nat Struct Biol 1999;6:222-7
  • Colledge M, Scott JD. AKAPs: from structure to function. Trends Cell Biol 1999;6:216-22
  • Rossi EA, Goldenberg DM, Cardillo TM, et al. Stably tethered multifunctional structures of defined composition made by the dock and lock method for use in cancer targeting. Proc Natl Acad Sci USA 2006;103:6841-6
  • Hodneland CD, Lee YS, Min DH, Mrksich M. Selective immobilization of proteins to self-assembled monolayers presenting active site-directed capture ligands. Proc Natl Acad Sci USA 2003;99:5048-52
  • Deyev SM, Waibel R, Lebedenko EN, et al. A. Design of multivalent complexes using the barnase-barstar module. Nat Biotechnol 2003;21:1486-92
  • Backer MV, Gaynutdinov TI, Patel V, et al. Adapter protein for site-specific conjugation of payloads for targeted drug delivery. Bioconj Chem 2004;15:1021-9
  • Rossi EA, Goldenberg DM, Cardillo TM, et al. Novel design of multivalent anti-CD20 humanized antibodies as improved lymphoma therapeutics. Cancer Res 2008;68:8384-92

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