Recombinant proteins and genomics in cancer therapy

  • Kapil Mehta
  • Kishor Gohil
  • Bharat B. Aggarwal


Recently published sequence of the complete human genome represents a major milestone in the era of the modern molecular biology [132, 318]. The sequencing of approximately 3.2 billion nucleotides of the human genome, encoding an estimated 100 000 proteins, signifies the first step down the long road. Gene identification does not necessarily translate into an understanding of gene function. Although mapping and cloning of several genes have linked them to heritable genetic disorders, the normal function of a majority of these genes remains unknown. Recombinant DNA technology has made it possible to generate large amounts of many biologically active proteins and to delineate their functions. The novelty of recombinant technology is the precision and efficiency with which scientists can manipulate the single gene. The ability to isolate human genes and insert them into microorganisms, which then produce human proteins, thereby serving as biological factories, has revolutionized the field of biology.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Aebersold R, Rist B, Gygi SP. Quantitative proteome analysis: methods and applications. Ann NY Acad Sci 2000; 919: 33–47PubMedGoogle Scholar
  2. 2.
    Aggarwal BB, Gutterman JU, eds. Human Cytokines: Handbook for Basic and Clinical Research, Boston (USA). Blackwell Scientific Publications, 1992.Google Scholar
  3. 3.
    Aggarwal BB, Pocsik E. Cytokines: from clone to clinic. Arch Biochem Biophys 1992; 292: 335–59.PubMedGoogle Scholar
  4. 4.
    Aggarwal BB, Puri R. Common and uncommon features of cytokines and cytokine receptors: an overview. In: Aggarwal BB, Puri R, eds. Human Cytokines: Their Role in Disease and Therapy. Oxford: Blackwell Science, 1994: 3–24.Google Scholar
  5. 5.
    Aggarwal BB. Tumour necrosis factors receptor associated signalling molecules and their role in activation of apoptosis, JNK and NF-kappaB. Ann Rheum Dis. 2000; 59 (Suppl. 1): i6–16.Google Scholar
  6. 6.
    Aggarwal BB, ed. Human Cytokines: Handbook for Basic Clinical Research. Blackwell Sciences, MA, 1998.Google Scholar
  7. 7.
    Ahuja SK, Murphy PM. Molecular piracy of mammalian interleukin-8 receptor type B by herpes virus saimiri. J Biol Chem 1993; 268: 20691–4.PubMedGoogle Scholar
  8. 8.
    Akira S, Taga T, Kishimoto T. Interleukin-6 in biology and medicine. Adv Immunol 1993; 54: 1–78.PubMedGoogle Scholar
  9. 9.
    Alizadeh AA, Ross DT, Perou CM, van De Rijn M. Towards a novel classification of human malignancies based on gene expression patterns. J Pathol 2001; 195: 41–52.PubMedGoogle Scholar
  10. 10.
    Alizadeh A, Eisen M, Davis RE. The lymphochip: a specialized cDNA microarray for the genomic-scale analysis of gene expression in normal and malignant lymphocytes. Cold Spring Harb Symp Quant Biol 1999; 64: 71–8.PubMedGoogle Scholar
  11. 11.
    Alton K, Stabinsky Y, Richards R et al. Production, characterization and biological effects of recombinant DNA derived human IFN-a and IFN-a analogues. In: De Maeyer E, Schellekens H, eds. The Biology of Interferon System. Amsterdam: Elsevier/North-Holland, 1983; 119–127.Google Scholar
  12. 12.
    Ambrus JL, Pippin J, Joseph A et al. Identification of a cDNA for a human high molecular weight B-cell growth factor. Proc Natl Acad Sci USA 1993; 90: 6330–4.PubMedGoogle Scholar
  13. 13.
    Andus T, Gross V, Holstege A et al. High concentrations of soluble tumor necrosis factor receptors in ascites. Hepatology 1992; 16: 749–55.PubMedGoogle Scholar
  14. 14.
    Apelgren LD, Zimmerman DL, Briggs SL, Bumol TF. Antitumor activity of the monoclonal antibody-vinca alkaloid immunoconjugate LY203725 in a nude mouse model of human ovarian cancer. Cancer Res 1990; 50: 3540–4.PubMedGoogle Scholar
  15. 15.
    Arai K, Lee F, Miyajima A et al. Cytokines: coordinators of immune and inflammatory responses. Annu Rev Biochem 1990; 59: 783–836.PubMedGoogle Scholar
  16. 16.
    Arai N, Nomura D, Villaret D et al. Complete nucleotide sequence of the chromosomal gene for human interleukin 4 and its expression. J Immunol 1989; 142: 274–82.PubMedGoogle Scholar
  17. 17.
    Arend WP. Interleukin-1 receptor antagonist. Adv Immunol 1993; 54: 167–227.PubMedGoogle Scholar
  18. 18.
    Bajorin DF, Cheung NKV, Houghton AN. Macrophage colony stimulating factor: biological effects and potential applications for cancer therapy. Semin Hematol 1991; 28: 42–8.PubMedGoogle Scholar
  19. 19.
    Baltathakis I, Alcantara O, Boldt DH. Expression of different NF-kappaB pathway genes in dendritic cells (DCs) or macrophages assessed by gene expression profiling. J Cell Biochem 2001; 83: 281–90.PubMedGoogle Scholar
  20. 20.
    Batra JK, Kasprzyk PG, Bird RE, Pastan I, King RC. Recombinant anti-erbB2 immunotoxins containing Pseudomonas exotoxin. Proc Natl Acad Sci USA 1992; 89: 5867–71.PubMedGoogle Scholar
  21. 21.
    Baynes RD, Reddy GK, Shih YJ, Skikne BS, Cook JD. Serum form of the erythropoietin receptor identified by a sequence-specific peptide. Blood 1993; 82: 2088–95.PubMedGoogle Scholar
  22. 22.
    Baselga J. Clinical trials of Herceptin (R) (trastuzumab) Eur J Cancer 2001; 37: S18 - S24.Google Scholar
  23. 23.
    Bell R. Duration of therapy in metastatic breast cancer: management using Herceptin. Anti-Cancer Drugs 2001; 12: 561–8.PubMedGoogle Scholar
  24. 24.
    Blumberg H, Conklin D, Xu WF et al. Interleukin-20: discovery, receptor identification, and role in epidermal function. Cell 2001; 104: 9–19.PubMedGoogle Scholar
  25. 25.
    Brinkmann U, Pai LH, FitzGerald DH, Willingham MC, Pastan I. B3(Fv)-PE38KDEL, a single chain immunotoxin that causes complete regression of human carcinoma in mice. Proc Natl Acad Sci USA 1991; 88: 8616–20.PubMedGoogle Scholar
  26. 26.
    Brinkmann U, Reiter Y, Jung SH, Lee B, Pastan I. A recombinant immunotoxin containing a disulfide-stabalized Fv fragment. Proc Natl Acad Sci USA 1993; 90: 7538–42.PubMedGoogle Scholar
  27. 27.
    Brown F. From Jenner to genes–the new vaccines. Lancet 1990; 335: 587–90.PubMedGoogle Scholar
  28. 28.
    Brown PO, Botstein D. Exploring the new world of the genome with DNA microarrays. Nat Genet 1999; 21: 33–7.PubMedGoogle Scholar
  29. 29.
    Broxmeyer HE, Benninger L, Cooper S, Huge N, Benjamin RS, Vadhan-Raj S. Effects of in vivo treatment with PIXY321 on proliferation kinetics of bone marrow and blood myeloid progenitor cells in patients with sarcoma. Exp Hematol 1995; 23: 335–40.PubMedGoogle Scholar
  30. 30.
    Campbell HD, Tucker WQJ, Hort Y et al. Molecular cloning, nucleotide sequence, and expression of gene encoding human eosinophil differentiation factor (IL-5). Proc Natl Acad Sci USA 1987; 84: 6629–33.PubMedGoogle Scholar
  31. 31.
    Cantell K, Hirvonen S, Mogensen KT, Pyhala L. Human leukocyte interferon: production, purification, stability, and animal experiments. In Vitro Monograph 1974; 3: 35–8.PubMedGoogle Scholar
  32. 32.
    Carter P, Presta L, Gorman CM et al. Humanization of antip185HER2 antibody for human cancer therapy. Proc Natl Acad Sci USA 1992; 89: 4285–9.PubMedGoogle Scholar
  33. 33.
    Chaffee S, Mary A, Stiehm ER, Girault D, Fischer A, Hershfield MS. IgG antibody response to ethylene glycol-modified adenosine deaminase in patients with ADA deficiency. J Clin Invest 1992; 89: 1643–51.PubMedCentralPubMedGoogle Scholar
  34. 34.
    Chari RVJ, Martell BA, Gross JL et al. Immunoconjugates containing novel maytansinoids: promising anticancer drugs. Cancer Res 1992; 52: 127–31.PubMedGoogle Scholar
  35. 35.
    Chaudhary VK, FitzGerald DJ, Adhaya S, Pastan I. Activity of a recombinant fusion protein between transforming growth factor-alpha and Pseudomonas toxin. Proc Natl Acad Sci USA 1987; 84: 4538–42.PubMedGoogle Scholar
  36. 36.
    Chaudhary VK, Queen C, Junghans RP, Waldman TA, FitzGerald DJ, Pastan I. A recombinant immunotoxin consisting of two antibody variable domains fused to Pseudomonas exotoxin. Nature 1989; 339: 394–6.PubMedGoogle Scholar
  37. 37.
    Chong CF, Scuderi P, Grimes WJ et al. Tumor targets stimulate IL-2 activated killer cells to produce IFN-gamma and TNF. J Immunol 1989; 142: 2133–9.PubMedGoogle Scholar
  38. 38.
    Clackson T, Hoogenbbom HR, Griffiths AD, Winter G. Making antibody fragments using phage display libraries. Nature 1991; 352: 624–8.PubMedGoogle Scholar
  39. 39.
    Clark BD, Collins KL, Gandy MS, Webb AC, Auron PE. Genomic sequence for human interleukin-1 beta gene. Nucleic Acid Res 1986; 14: 7897–914.PubMedGoogle Scholar
  40. 40.
    Claverie JM. Gene number. What if there are only 30,000 human genes ? Science 2001; 291: 1255–7.PubMedGoogle Scholar
  41. 41.
    Coller HA, Grandori C, Tamayo P et al. Expression analysis with oligonucleotide microarrays reveals that MYC regulates genes involved in growth, cell cycle, signaling, and adhesion. Proc Natl Acad Sci USA 2000; 97: 3260–5.PubMedGoogle Scholar
  42. 42.
    Colombo MP, Forni G. Cytokine gene transfer in tumor inhibition and tumor therapy: where are we now? Immunol Today 1994; 15: 48–51.PubMedGoogle Scholar
  43. 43.
    Colombo MP, Modesti A, Parmiani G, Forni G. Local cytokine availability elicits tumor rejection and systemic immunity through granulocyte-T lymphocyte cross talk. Cancer Res 1992; 52: 4853–7.PubMedGoogle Scholar
  44. 44.
    Conry RM, LoBugilio A, Wright M et al. Characterization of a messenger RNA polynucleotide vaccine vector. Cancer Res 1995; 55: 1397–400.PubMedGoogle Scholar
  45. 45.
    Conry RM, LoBuglio AF, Kantor J et al. Immune response to a carcinoembryonic antigen polynucleotide vaccine. Cancer Res 1994; 54: 1164–8.PubMedGoogle Scholar
  46. 46.
    Cosman D, Lyman SD, Idzerda RL et al. A new cytokine receptor superfamily. Trends Biochem Sci 1990; 7: 265–70.Google Scholar
  47. 47.
    Coussens L, Yang-Feng TL, Liau YC et al. Tyrosine kinase recptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science 1985; 230: 1132–9.PubMedGoogle Scholar
  48. 48.
    Crawford J, Ozer H, Stoller R. Reduction by granulocyte colony stimulating factor of fever and neutropenia induced by chemotherapy in patients with small cell lung cancer. N Engl J Med 1991; 325: 164–70.PubMedGoogle Scholar
  49. 49.
    Cruikshank WW, Kornfeld H, Center DM. Interleukin-16. J Leukoc Biol 2000; 67: 757–66.PubMedGoogle Scholar
  50. 50.
    Curtis BM, Williams DE, Broxmeyer HE et al. Enhanced hematopoietic activity of a human granulocyte/macrophage colony stimulating factor-interleukin-3 fusion protein. Proc Natl Acad Sci USA 1991; 88: 5809–13.PubMedGoogle Scholar
  51. 51.
    Cwirla SE, Peters EA, Barrett RW, Dower WJ. Peptides on phage: a vast library of peptides for identifying ligands. Proc Natl Acad Sci USA 1990; 87: 6378–82.PubMedGoogle Scholar
  52. Das M, Burge CB, Park E, Colinas J, Pelletier J. Assessment of the total number of human transcription units. Genomics 2001; 77: 71–8.Google Scholar
  53. 54.
    Daughaday WH, Rotwein P. Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations. Endocr Rev 1989; 10: 68–91.PubMedGoogle Scholar
  54. 55.
    Debinski W, Puri RK, Kreitman RJ, Pastan I. A wide range of human cancers express interleukin-4 receptors that can be targeted with chimeric toxin composed of IL-4 and Pseudomonas exotoxin. J Biol Chem 1993; 268: 14065–70.PubMedGoogle Scholar
  55. 56.
    Derynck R. The physiology of transforming growth factor-ß. Adv Cancer Res 1992; 58: 27–52.PubMedGoogle Scholar
  56. 57.
    Derynck R, Jarrett JA, Chen EY et al. Human transforming growth factor-beta cDNA sequence and expression in tumor cell lines. Nature 1985; 316: 701–5.PubMedGoogle Scholar
  57. 58.
    Dinarello CA. The interleukin-1 family: 10 years of discovery. FASEB J 1994; 8: 1314–25.PubMedGoogle Scholar
  58. 59.
    Dinarello CA. Interleukin-1 and interleukin-1 antagonism. Blood 1991; 77: 1627–52.PubMedGoogle Scholar
  59. 60.
    DiStefano PS, Johnson EM. Identification of a truncated form of nerve growth factor receptor. Proc Natl Acad Sci USA 1988; 85: 270–4.PubMedGoogle Scholar
  60. 61.
    Dorai H, McCartney JE, Hudziak RM et al. Mammalian cell expression of a single chain Fv (sFv) antibody protein and their C-terminal fusions with interleukin-2 and other effector domains. Biotechnology 1995, 12: 890–7.Google Scholar
  61. 62.
    Downing JR, Rousesel MF, Sherr CJ. Ligand and protein kinase C downmodulate the colony stimulating factor 1 receptor by independent mechanism. Mol Cell Biol 1989; 9: 2890–6.PubMedCentralPubMedGoogle Scholar
  62. 63.
    Dranoff G, Mulligan C. Gene transfer as cancer therapy. Adv Immunol 1995; 58: 417–54.PubMedGoogle Scholar
  63. 64.
    Du XX, Williams DA. Interleukin-11: a multifunctional growth factor derived from the hematopoietic microenvironment. Blood 1994; 83: 2023–30.PubMedGoogle Scholar
  64. 65.
    Edman JC, Halliwell RA, Valenzuela P, Goodman HM, Rutter WJ. Synthesis of hepatitis B surface and core antigens in E. coli. Nature 1981; 291: 503–6.Google Scholar
  65. 66.
    Edwards GM, DeFeo-Jones D, Tai JY et al. Epidermal growth factor receptor binding is affected by structural determinants in the toxin domain of transforming growthGoogle Scholar
  66. factor-alpha-Pseudomonas exotoxin fusion protein. Mol Cell Biol 1989; 9: 2860–7.Google Scholar
  67. 67.
    Eschbach JW, Egrie JC, Downing MR, Browne JK, Adamson JW. Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. N Engl J Med 1987; 316: 73–8.PubMedGoogle Scholar
  68. 68.
    Estrov Z, Kurzrock R, Wetzler M et al. Suppression of chronic myelogenous leukemia colony growth by IL-1 receptor antagonist and soluble IL-1 receptors: a novel application for inhibitors of IL-1 activity. Blood 1991; 78: 1476–84.PubMedGoogle Scholar
  69. 69.
    Fantes KH, Allen GJ. Specific activity of pure human interferons and a non-biological method for estimating the purity of highly purified interferon preparations. Interferon Res 1981; 1: 465–72.Google Scholar
  70. 70.
    Fehniger TA, Caliguiri MA. Interleukin-15; biology and relevance to human diseases. Blood 2001; 97: 14–32.PubMedGoogle Scholar
  71. 71.
    Feng GS, Gray PW, Shepard HM, Taylor MW. Antiproliferative activity of a hybrid protein between interferon-and tumor necrosis factor-ß. Science 1988; 241: 1501–3.PubMedGoogle Scholar
  72. 72.
    Fenton RG, Taub DD, Kwak LW, Smith MR, Longo DL. Cytotoxic T cell response and in vivo protection against tumor cells harboring activated ras prot-oncogenes. J Natl Cancer Inst 1993; 85: 1294–302.PubMedGoogle Scholar
  73. 73.
    Fernandez-Botran R. Soluble cytokine receptors: their role in immunoregulation. FASEB J 1991; 5: 2567–4.PubMedGoogle Scholar
  74. 74.
    Fernadez-Borton R, Vitetta ES. A soluble, high affinity interleukin-4 binding protein is present in the biological fluids of mice. Proc Natl Acad Sci USA 1990; 87: 4202–6.Google Scholar
  75. 75.
    FitzGerald DJ, Bjorn MJ, Ferris R et al. Antitumor activity of an immunotoxin in nude mouse model of human ovarian cancer. Cancer Res 1987; 47: 1407–10.PubMedGoogle Scholar
  76. 76.
    FitzGerald DJ, Pastan I. A recombinant immunotoxin consisting of two antibody variable domains fused to Pseudomonas exotoxin. Nature 1989; 339: 394–7.PubMedGoogle Scholar
  77. 77.
    Fletcher FA, Williams DE. Recent progress in the discovery and invention of novel hematopoietic cytokines. Crit Rev Oncol Hematol 1992; 13: 1–15.PubMedGoogle Scholar
  78. 78.
    Fujiwara K, Yoshino T, Miyake K, Ohara N, Akagi T. Expression of lymphocyte adhesion molecule (CD44) in malignant lymphomas. Relevance to primary site, histological subtype and clinical stage. Acta Med Okayama 1993; 47: 215–22.PubMedGoogle Scholar
  79. 79.
    Fukunaga R, Seto Y, Mizushima S, Nagata S. Three different mRNAs encoding human granulocyte colony-stimulating factor receptor. Proc Natl Acad Sci USA 1990; 87: 8702–6.PubMedGoogle Scholar
  80. 80.
    Fulton RJ, Uhr JW, Vitetta ES. In vivo therapy of the BCL1 tumor: effect of immunotoxin valency and deglycosylation of the ricin A chain. Cancer Res 1988; 48; 2626–31.PubMedGoogle Scholar
  81. 81.
    Furr BJA, Hutchinson FG. A biodegradable delivery system for peptides: preclinical experience with the gonadotropinreleasing hormone agonist Zoladex. J Controlled Release 1992; 21: 117–28.Google Scholar
  82. 82.
    Furukawa Y, Ohata M, Miura Y, Saito M. Interleukin-1 production by monocytic leukemia cells and its role in coagulation abnormalities. Leuk Res 1991; 15: 1133–7.PubMedGoogle Scholar
  83. 83.
    Furutani Y, Notake M, Fukui T et al. Complete nucleotide sequence of the gene for human interleukin-1 alpha. Nucleic Acid Res 1986; 143: 3167–79.Google Scholar
  84. 84.
    Gabrilove J, Jakubowski A, Grous J et al. Initial results of a study of rhG-CSF in cancer patients. Exp Hematol 1987; 15: 461–5.Google Scholar
  85. 85.
    Gadina M, Hilton D, Johnston JA et al. Signaling by type I and II cytokine receptors: ten years after. Curr Opin Immunol2001; 13: 363–73.Google Scholar
  86. 86.
    Gallagher G, Dickensheets H, Eskdale J, Izotova LS, Mirochnitchenko OV, Peat JD, Vazquez N, Pestka S, Donnelly RP, Kotenko SV. Cloning, expression and initialGoogle Scholar
  87. characterization of interleukin-19 (IL-19), a novel homologue of human interleukin-10 (IL-10). Genes Immun. 2000; 1: 442–50.Google Scholar
  88. 87.
    Ganser A, Lindemann A, Seipelt G et al. Clinical effects of recombinant interleukin-3. Am J Clin Oncol 1991; 14: 51–63.Google Scholar
  89. 88.
    Gatanaga T, Hwang C, Kohr W et al. Purification and characterization of an inhibitor (soluble TNF receptor) for TNF and lymphotoxin obtained from the serum infiltrates of human cancer patients. Proc Natl Acad Sci USA 1990; 87: 8781–4.PubMedGoogle Scholar
  90. 89.
    Ghetie MA, Vitetta ES. Recent developments in immunotoxin therapy. Curr Opin Immunol 1994; 6: 707–14.PubMedGoogle Scholar
  91. 90.
    Giri JG, Anderson DM, Kumaki S, Park LS, Grabstein KH, Cosman D. IL-15, a novel T cell growth factor that shares activities and receptor components with IL-2. J Leukoc Biol 1995; 57: 763–6.PubMedGoogle Scholar
  92. 91.
    Godon C, Lagniel G, Lee J et al. The H2O2 stimulon in Saccharomyces cerevisiae. J Biol Chem 1998; 273: 22480–9.PubMedGoogle Scholar
  93. 92.
    Golub TR, Slonim DK, Tamayo P et al. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 1999; 286: 531–7.PubMedGoogle Scholar
  94. 93.
    Golumbek PT, Lazenby AJ, Levitsky HI et al. Treatment of established renal cell cancer by tumor cells engineered to secrete interleukin-4. Science 1991; 254: 713–16.PubMedGoogle Scholar
  95. 94.
    Goodnough LT, Rudnick S, Price TH et al. Increased preoperative collection of autologous blood with recombinant human erythropoietin therapy. N Engl J Med 1989; 321: 1163–8.PubMedGoogle Scholar
  96. 95.
    Goodwin R, Friend D, Ziegler SF et al. Cloning of the murine and human interleukin receptors: demonstration of a soluble form and homology to a new receptor superfamily. Cell 1990; 60: 941–51.PubMedGoogle Scholar
  97. 96.
    Goodwin RG, Lupton S, Schmierer A et al. Human interleukin-7: molecular cloning and growth factor activity on human and murine B-lineage cells. Proc Natl Acad Sci USA 1989; 86: 302–6.PubMedGoogle Scholar
  98. 97.
    Gorman CM. Mammalian cell expression. Curr Opin Biotech 1990; 1: 36–43.PubMedGoogle Scholar
  99. 98.
    Gospodarowicz D. Fibroblast growth factor. Crit Rev Oncog 1989; 1: 1–26.PubMedGoogle Scholar
  100. 99.
    Gough NM, Gearing DP, King JA et al. Molecular cloning and expression of the human homologue of the murine gene encoding myeloid leukemia inhibitory factor. Proc Natl Acad Sci USA 1988; 85: 2623–7.PubMedGoogle Scholar
  101. 100.
    Grabstein KH, Eisenman J, Shanebeck K et al. Cloning of a novel T cell growth factor that interacts with the ß chain of the interleukin-2 receptor. Science 1994; 264: 965–8.PubMedGoogle Scholar
  102. 101.
    Gray A, Dull TJ, Ullrich A. Nucleotide sequence of epidermal growth factor cDNA predicts a 128,000-molecular weight protein precursor. Nature 1983; 303: 722–5.PubMedGoogle Scholar
  103. 102.
    Gray PW, Aggarwal BB, Benton C et al. Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumor necrosis factor activity. Nature 1984; 312: 721–4.PubMedGoogle Scholar
  104. 103.
    Gray PW, Goeddel DV. Structure of the human immune interferon cDNA. Nature 1982; 298: 859–63.PubMedGoogle Scholar
  105. 104.
    Griffin JD, Rambaldi A, Vallenga E, Young DC, Ostapovicz D, Cannistra SA. Secretion of interleukin-1 by acute myeloblastic leukemia cells in vitro induces endothelial cells to secrete colony stimulating factors. Blood 1987; 70: 1218–21.PubMedGoogle Scholar
  106. 105.
    Griffin TW, Richardson C, Houston LL, LePage D, Bogden A, Raso V. Antitumor activity of intraperitoneal immunotoxins in a nude mouse model of human malignant mesothelioma. Cancer Res 1987; 47: 4266–70.PubMedGoogle Scholar
  107. 106.
    Grossbard ML, Press OW, Appelbaum FR, Bernstein ID, Nadler LM. Monoclonal antibody-based therapies of leukemia and lymphoma. Blood 1992; 80: 863–78.PubMedGoogle Scholar
  108. 107.
    Gubler U, Chua AO, Schoenhaut DS et al. Coexpression of two distinct genes is required to generate secreted, bioactive cytotoxic lymphocyte maturation factor. Proc Natl Acad Sci USA 1991; 88: 4143–7.PubMedGoogle Scholar
  109. 108.
    Gunther N, Betzel C, Weber W. The secreted form of the epidermal growth factor receptor. J Biol Chem 1990; 265: 22082–5.PubMedGoogle Scholar
  110. 109.
    Gurney AL, Marsters SA, Huang RM. Identification of a new member of the tumor necrosis factor family and its receptor, a human ortholog of GITR. Curr Biol 1999; 9: 215–18.PubMedGoogle Scholar
  111. 110.
    Gutterman JU, Blumenshein GR, Alexanian R et al. Leukocyte interferon-induced tumor regression in human metastatic breast cancer, multiple myeloma, and malignant lymphoma. Ann Intern Med 1980; 93: 399–406.PubMedGoogle Scholar
  112. 111.
    Gutterman JU, Fine S, Quesada J et al. Recombinant leukocyte A interferon: pharmacokinetics, single-dose tolerance, and biological effects in cancer patients. Ann Intern Med 1982; 96: 549–56.PubMedGoogle Scholar
  113. 112.
    Gutterman JU. Cytokine therapeutics: lessons from interferon alpha. Proc Natl Acad Sci USA 1994; 91: 1198–205.PubMedGoogle Scholar
  114. 113.
    Hall WA, Merill MJ, Walbridge S, Youle RJ. Epidermal growth factor receptors on ependymomas and other brain tumors. J Neurosurg 1990; 72: 641–6.PubMedGoogle Scholar
  115. 114.
    Han ZC, Caen JP. Cytokines acting on committed hematopoietic progenitors. Clin Hematol 1994; 7: 65–89.Google Scholar
  116. 115.
    Heaney ML, Golde DW. Soluble hormone receptors. Blood 1993; 82: 1945–8.PubMedGoogle Scholar
  117. 116.
    Heldin C-H. Structural and functional studies on platelet derived growth factor. EMBO J 1992; 11: 4251–9.PubMedGoogle Scholar
  118. 117.
    Heller J. Polymers for controlled parenteral delivery of peptides and proteins. Adv Drug Deliv Rev 1993; 10: 163–204.Google Scholar
  119. 118.
    Heller RA, Song K, Fan N et al. The p70 tumor necrosis factor receptor mediates cytotoxicity. Cell 1992; 70: 47–56.PubMedGoogle Scholar
  120. 119.
    Hellstrom I, Hellstrom KE. Anti-idiotypic antibodies as tumor vaccines. In: Woodrow GC, Levine MM, eds. New Generation Vaccines. Marcel Dekker: New York, 1990; 863–70.Google Scholar
  121. 120.
    Hersch EM, Metch BS, Muggia FM et al. Phase II studies of recombinant tumor necrosis factor alpha in patients with malignant disease: a summary of the Southwest Oncology Group experience. J Immunother 1991; 10: 426–31.Google Scholar
  122. 121.
    Hill ADK, Redmond HP, McCarthy J, Croke DT, Grace PA, Bouchier-Hayes D. Antineoplastic effects of granulocyte macrophage colony stimulating factor. Br J Surg 1992; 79: 459 (abstract).Google Scholar
  123. 122.
    Hill ADK, Redmond HP, Croke DT, Grace PA, BouchierHayes D. Cytokines in tumor therapy. Br J Surg 1992; 79: 990–7.PubMedGoogle Scholar
  124. 123.
    Hill CS, Treisman R. Transcriptional regulation by extra-cellular signals: mechanisms and specificity. Cell 1995; 80: 199–211.PubMedGoogle Scholar
  125. 124.
    Hinman LM, Hamann PR, Wallace R, Menedez TA, Durr FE, Upeslacis J. Preparation and characterization of monoclonal antibody conjugates of the calicheamicins: a novel and potent family of antitumor antibiotics. Cancer Res 1993; 53: 3336–42.PubMedGoogle Scholar
  126. 125.
    Hirano T, Yasukawa K, Harada H et al. Complementary DNA for a novel human interleukin (BSF-2) that induces B-lymphocytes to produce immunoglobulin. Nature 1986; 324: 73–6.PubMedGoogle Scholar
  127. 126.
    Hitzeman RA, Chen CY, Hagie FE, Lugovoy JM, Singh A. Yeast: an alternative organism for foreign protein production. In: Bollon AP, ed. Recombinant DNA Products. Boca Raton, FL: CRC Press, 1983; 47–65.Google Scholar
  128. 127.
    Hock H, Dorsch M, Kunzendorf U et al. Vaccination with tumor cells genetically engineered to produce differentGoogle Scholar
  129. Horuk R. The interleukin-8-receptor family: from chemokines to malaria. Immunol Today 1994; 15: 169–74.Google Scholar
  130. 129.
    Hoshino T, Kawase Y, Okamoto M et al. IL-18 transgenic mice: in vivo evidence of a broad role for IL-18 modulating immune function. J Immunol 2001; 166: 7014–18.PubMedGoogle Scholar
  131. 130.
    Ideker T, Thorsson V, Ranish JA. Integrated genomic and proteomic analyses of a systematically perturbed metabolic network. Science 2001; 292: 929–34PubMedGoogle Scholar
  132. 131.
    Ihle JN. Signaling by the cytokine receptor superfamily in normal and transformed hematopoietic cells. Adv Cancer Res 1996; 68: 23–65.PubMedGoogle Scholar
  133. 132.
    International Human Genome Sequence Consortium. Initial sequencing and analysis of the human genome. Nature 2001; 409: 860.Google Scholar
  134. 133.
    Itoh N, Yonehara S, Ishii A et al. The polypeptide encoded by the cDNA for the human cell surface antigen Fas can mediate apoptosis. Cell 1991; 66: 233–43.PubMedGoogle Scholar
  135. 134.
    Jacobs AJ, Fer M, Su FM et al. A phase I trial of a rhenium 186-labeled monclonal antibody administered intraperitoneal in ovarian carcinoma: toxicity and clinical response. Obstet Gynecol 1993; 82: 586–93.PubMedGoogle Scholar
  136. 135.
    Jacobs K, Shoemaker C, Rudersdorf R et al. Isolation and characterization of genomic and cDNA clones of human erythropoietin. Nature 1985; 313: 806–10.PubMedGoogle Scholar
  137. 136.
    Jinno Y, Chaudhary VK, Kondo T, Adhya S, FitzGerald D, Pastan I. Mutational analysis of domain I of Pseudomonas exotoxin. J Biol Chem 1988; 263: 13203–7.PubMedGoogle Scholar
  138. 137.
    Jurcic JC, Scheinberg DA, Houghton AN. Monoclonal antibody therapy of cancer. In: Pinedo HM, Longo DL, Chabner BA, eds. Cancer Chemotherapy and Biological Response Modifiers Annual 14. Amsterdam: Elsevier, 1993: 129–49.Google Scholar
  139. 138.
    Jurcic JG, Scheinberg DA. Recent developments in the radiotherapy of cancer. Curr Opin Immunol 1994; 6: 715–21.PubMedGoogle Scholar
  140. 139.
    Kalinkowich A, Engelmann H, Harpaz N et al. Elevated serum levels of soluble tumor necrosis factor in patients with HIV infection. Clin Exp Immunol 1992; 89: 351–5.Google Scholar
  141. 140.
    Kaplan EH, Leslie WT. Cutaneous T-cell lymphomas. Curr Opin Oncol 1993; 5: 812.PubMedGoogle Scholar
  142. 141.
    Kaptain S, Tan LK, Chen BY. Her-2/neu and breast cancer. Diag Mol Pathol 2001; 10: 139–52.Google Scholar
  143. 142.
    Karp JE, Broder S. New directions in molecular medicine. Cancer Res 1994; 54: 653–65.PubMedGoogle Scholar
  144. 143.
    Katoh M, Yazaki Y, Sugimura T, Terada M. C- erbB3 gene encodes secreted as well as transmembrane receptor tyrosine kinase. Biochem Biophys Res Commun 1993; 192: 1189–97.PubMedGoogle Scholar
  145. 144.
    Katre NV. The conjugation of proteins with polyethylene glycol and other polymers: altering properties of proteins to enhance their therapeutic potential. Adv Drug Deliv Rev 1993; 10: 91–114.Google Scholar
  146. 145.
    Kawasaki ES, Ladner MB, Wang AM et al. Molecular cloning of a complementary DNA encoding human macrophage-specific colony stimulating factor (CSF-1). Science 1985; 230: 291–6.PubMedGoogle Scholar
  147. 146.
    Klein B, Wijdenes J, Xang XG et al. Murine anti-interleukin-6 monoclonal antibody therapy for a patient with plasma cell leukemia. Blood 1991; 78: 1198–204.PubMedGoogle Scholar
  148. 147.
    Koff WC, Paige C, Gutterman J, Fidler IJ. Efficient activation of human blood monocytes to a tumoricidal state by liposomes containing human recombinant gamma interferon. Cancer Immunol Immunother 1985; 19: 85–9.PubMedGoogle Scholar
  149. 148.
    Koppel GA. Recent advances with monoclonal antibody drug targeting for the treatment of human cancer. Bioconjug Chem 1990; 1: 13–23.PubMedGoogle Scholar
  150. 149.
    Kotenko SV, Izotova LS, Mirochnitchenko OV et al. Identification, cloning, and characterization of a novel soluble receptor that binds IL-22 and neutralizes its activity. J Immunol 2001; 166: 7096–103.PubMedGoogle Scholar
  151. 150.
    Kozak RW, Lorberboum GH, Jone L et al. IL-2-PE40 prevents the development of tumors in mice injected with IL-2 receptor expressing EL4 transfectant tumor cells. J Immunol 1990; 145: 2766–71.PubMedGoogle Scholar
  152. 151.
    Krammer PH. CD95’s deadly mission in the immune system. Nature 2000; 407: 789–95.PubMedGoogle Scholar
  153. 152.
    Kreeger KY. Cancer immunotherapies: an old idea sparks new studies, industry interest. The Scientist 1995; 9: 1.Google Scholar
  154. 153.
    Kreitman RJ, Bailon P, Cahudhary VK, FitzGerald DJ, Pastan I. Recombinant immunotoxins containing antiTac(Fv) and derivatives of Pseudomonas exotoxin produce complete regression in mice of interleukin-2 receptor-expressing human carcinoma. Blood 1994; 83: 426–34.PubMedGoogle Scholar
  155. 154.
    Kreitman RJ, Chang CN, Hudson DV, Queen C, Bailon P, Pastan I. Anti-Tac(Fab)-PE40, a recombinant double chain immunotoxin which kills interleukin-2 receptor bearing cells and induces complete remission in an in vivo tumor model. Int J Cancer 1994; 57: 856–64.PubMedGoogle Scholar
  156. 155.
    Kreitman RJ, Chaudhary VK, Waldman T, Willingham MC, FitzGerald DJ, Pastan I. The recombinant immunotoxin anti-Tac (Fv)-Pseudomonas exotoxin 40 is cytotoxic towards peripheral blood malignant cells from patients with adult T cell leukemia. Proc Natl Acad Sci USA 1990; 87: 8291–5.PubMedGoogle Scholar
  157. 156.
    Kreitman RJ, Hansen HJ, Jones AL, FitzGerald D, Goldenberg DM, Pastan I. Pseudomonas exotoxin-based immunotoxin containing the antibody LL2 or LL2 Fab’ induce regression of subcutaneous human B-cell lymphoma in mice. Cancer Res 1993; 53: 819–25.PubMedGoogle Scholar
  158. 157.
    Lachman LB, Dinarello CA, Llansa LD, Fidler IJ. Natural and recombinant human interleukin-1 is cytotoxic for human melanoma cells. J Immunol 1986; 136: 3098–102.PubMedGoogle Scholar
  159. 158.
    Lalli E, Sassone-Corsi P. Signal transduction and gene regulation: the nuclear response to cAMP. J Biol Chem 1994; 269: 17359–62.PubMedGoogle Scholar
  160. 159.
    Layton MJ, Cross BA, Metcalf D, Ward LD, Simpson RJ, Nicola NA. A major binding-protein for human leukemia inhibitory factor in normal mouse serum: identification as a soluble form of the cellular receptor. Proc Natl Acad Sci USA 1992; 89: 8616–20.PubMedGoogle Scholar
  161. 160.
    Lee VHL. Peptide and protein drug delivery: opportunities and challenges. Pharm Int 1986: 208–212.Google Scholar
  162. 161.
    Leitzel K, Teramoto Y, Sampson E et al. Elevated soluble cerb-2 antigen levels in the serum and effusions of a proportion of a breast cancer patients. J Clin Oncol 1992; 10: 1436–43.PubMedGoogle Scholar
  163. 162.
    Leonard WJ, Shores EW, Love PE. Role of the common cytokine receptor gamma chain in cytokine signaling and lymphoid development. Immunol Rev 1995; 148: 97–114.PubMedGoogle Scholar
  164. 163.
    Lewis R. End of century marks dawn of clinical trial era for cancer vaccines. Scientist 1995; 9: 15.Google Scholar
  165. 164.
    Lewis GD, Figari L, Fendly B, Carter P, Gorman C, Shepard M. Differential responses of human tumor cell lines to anti-p185HER2 monoclonal antibodies. Cancer Immunol Immunother 1993; 37: 255–63.PubMedGoogle Scholar
  166. 165.
    Lewis R. Herceptin earns recognition in breast cancer arsenal. Scientist 2001; 15: 10–11.Google Scholar
  167. 166.
    Li H, Chen J, Huang A et al. Cloning and characterization of IL-17B and IL-17C, two new members of the IL-17 cytokine family. Proc Natl Acad Sci USA 2000; 97: 773–8.PubMedGoogle Scholar
  168. 167.
    Lienard D, Ewalenko P, Delmotte JJ et al. High dose recombinant tumor necrosis factor alpha in combination with interferon gamma and melphalan in isolation perfusion of the limbs for melanoma and sarcoma. J Clin Oncol 1992; 10: 52–60.PubMedGoogle Scholar
  169. 168.
    Lim VS, DeGowin RL Zavala D et al. Recombinant human erythropoietin treatment in pre-dialysis patients. Ann Intern Med 1989; 110: 108–18.PubMedGoogle Scholar
  170. 169.
    Lipshutz RJ, Fodor SP, Gingeras TR, Lockhart DJ. High density synthetic oligonucleotide arrays. Nat Genet 1999; 21: 20–4.PubMedGoogle Scholar
  171. 170.
    Lippman SM, Parkinson DR, Itri LM et al. 13-Cis retinoic acid and interferon-a-2a: effective combination therapy for advanced squamous cell carcinoma of the skin. J Natl Cancer Inst 1992; 84: 235–41.Google Scholar
  172. 171.
    Lodato RF, Feig B, Akimaru K, Soma GI, Klostergaard J. Hemodynamic evaluation of recombinant human tumor necrosis factor (TNF), TNF-SAM2 and liposomal TNFSAM2 in an anesthetized dog model. J Immunother 1995; 17: 19–29.Google Scholar
  173. 172.
    Lorberboum GH, FitzGerald DJ, Chaudhary VK, Adhya S, Pastan I. Cytotoxic activity of an interleukin 2-Pseudomonas exotoxin chimeric protein produced in Escherichia coli. Proc Natl Acad Sci USA 1988; 85: 1922–6.Google Scholar
  174. 173.
    Lord MJ, Roberts LM, Robertus JD. Ricin: structure, mode of action, and some current applications. FASEB J 1994; 8: 201–8.PubMedGoogle Scholar
  175. 174.
    Lotze MT, Custer MC, Bolton ES, Wiebke EA, Kwakami Y, Rosenberg SA. Mechanisms of immunological antitumor activity: lessons from the laboratory and clinical application. Hum Immunol 1990; 28: 198–207.PubMedGoogle Scholar
  176. 175.
    Lotze MT, Matory YL, Rayner AA. Clinical effects and toxicity of interleukin-2 in patients with cancer. Cancer 1986; 58: 2764–72.PubMedGoogle Scholar
  177. 176.
    Lowman HB, Bass S, Simpson S, Wells JA. Selecting high affinity binding proteins by monovalent phage display. Biochemistry 1991; 30: 10832–8.PubMedGoogle Scholar
  178. 177.
    Luckow VA. In: Prokop A, Bajpai RK, Ho CS eds. Recombinant DNA Technology and Applications, McGraw-Hill Inc. 1991; 97–152.Google Scholar
  179. 178.
    Luckow VA, Summers MD. Trends in the development of baculovirus expression vectors. Biotechniques 1988; 6: 47–55.Google Scholar
  180. 179.
    Malik N, Kallestad JC, Gunderson NL et al. Molecular cloning, sequence analysis, and functional expression of a novel growth regulator, oncostatin M. Mol Cell Biol 1989; 9: 2847–53.PubMedCentralPubMedGoogle Scholar
  181. 180.
    Markussen J, Diers I, Engesgaard A et al. Soluble, prolonged acting insulin derivatives. II. Degree of protraction and crystallizability of insulins substituted in positions A17, B8, B27 and B30. Protein Eng 1987; 1: 215–23.PubMedGoogle Scholar
  182. 181.
    Marton MJ, DeRisi JL, Bennett HA et al. Drug target validation and identification of secondary drug target effects using DNA microarrays. Nat Med 1998; 4: 1293–301.PubMedGoogle Scholar
  183. 182.
    McLaughlin P, Cabanillas, F, Hagemeister FB et al. CHOPBleo plus interferon for stage IV low-grade lymphoma. Ann Oncol 1993; 4: 205–11.PubMedGoogle Scholar
  184. 183.
    Meredith RF, Khaxaeli MB, Lui T et al. Dose fractionation of radiolabeled antibodies in patients with metastatic colon cancer. J Nucl Med 1992; 33: 1648–53.PubMedGoogle Scholar
  185. 184.
    Meredith RF, Khazaeli MB, Plott WE et al. Phase I trial of iodine-131 chimeric B72.3 (human IgG4) in metastatic colorectal cancer. J Nucl Med 1992; 33: 23–9.PubMedGoogle Scholar
  186. 185.
    Miller L. Current status of G-CSF in support of chemotherapy and radiotherapy. Oncology 1993; 7: 67–88.PubMedGoogle Scholar
  187. 186.
    Milstein C. Monoclonal antibodies (review). Sci Am 1980; 243: 66–74.PubMedGoogle Scholar
  188. 187.
    Minty A, Chalon P, Derocq JM et al. Interleukin 13 is a new human lymphokine regulating inflammatory and immune responses. Nature 1993; 362: 248–50.PubMedGoogle Scholar
  189. 188.
    Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001; 19: 683–765.PubMedGoogle Scholar
  190. 189.
    Morgan AC, Comezoglu FT, Manger R, Jarvis B, Abrams PJ, Sivam G. Immunoconjugates of a protein-synthesisinhibiting drugs. In: Borrebaeck C, Larrick J, eds. Therapeutic Monoclonal Antibodies. New York: Stockton Press, 1990: 143–58.Google Scholar
  191. 190.
    Mori I, Hossain MJ, Takeda K et al. Impaired microglial activation in the brain of IL-18 gene-disrupted mice after neurovirulent influenza A virus infection. Virology 2001; 287: 163–70.PubMedGoogle Scholar
  192. 191.
    Mosley B, Beckman MP, March CJ et al. The murine interleukin-4 receptor: a molecular cloning and characterization of secreted and membrane-bound forms. Cell 1989; 59: 335–48.PubMedGoogle Scholar
  193. 192.
    Motoyshi K, Takaku F. Human monocytic colony stimulating factor, phase I/II clinical studies. In: Metelsmann R, Hermann F, eds. Hematopoietic Growth Factors in Clinical Applications. New York: Marcel Dekker, 1990; 161–75.Google Scholar
  194. 193.
    Mukaida N, Shiroo M, Matsushima K. Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8. J Immunol 1989; 143: 1366–71.PubMedGoogle Scholar
  195. 194.
    Mule JJ, Smith CA, Rosenberg SA. Interleukin 4 (B cell stimulatory factor 1) can mediate the induction of lymphokine activated killer activity directed against fresh tumor cells. J Exp Med 1987; 166: 792–8.PubMedGoogle Scholar
  196. 195.
    Mullberg J, Schooltink H, Stoyan T et al. The soluble interleukin-6 receptor is generated by shedding. Eur J Immunol 1993; 23: 473–80.Google Scholar
  197. 196.
    Nagao M, Masuda S, Abe S, Ueda M, Sasaki R. Production and ligand-binding characteristics of the soluble form of murine erythropoietin receptor. Biochem Biophys Res Commun 1992; 188: 888–97.PubMedGoogle Scholar
  198. 197.
    Nagata S, Tsuchiya M, Asano S et al. Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. Nature 1986; 319: 415–18.PubMedGoogle Scholar
  199. 198.
    Nakajima T, Yamamoto S, Cheng M et al. Soluble interleukin-6 receptor is released from receptor-bearing cell lines in vitro. Jpn J Cancer Res 1992; 83: 373–8.PubMedGoogle Scholar
  200. 199.
    Nakamura T, Nishizawa T, Hagiya M et al. Molecular cloning and expression of human hepatocyte growth factor. Nature 1989; 342: 440–3.PubMedGoogle Scholar
  201. 200.
    Nakanishi K, Yoshimoto T, Tsutsui H, Okamura H. Interleukin-18 is a unique cytokine that stimulates both Th1 and Th2 responses depending on its cytokine milieu. Cytokine Growth Factor Rev 2001; 12: 53–72.PubMedGoogle Scholar
  202. 201.
    Nakanishi K, Yoshimoto T, Tsutsui H, Okamura H. Interleukin-18 regulates both Th1 and Th2 responses. Annu Rev Immunol 2001; 19: 423–74.PubMedGoogle Scholar
  203. 202.
    Narazaki M, Yasukawa K, Saiton T et al. Soluble form of IL-6 signal transducing receptor component gp130 in human serum processing a potential to inhibit signals through membrane anchored gp130. Blood 1993; 82: 1120–6.PubMedGoogle Scholar
  204. 203.
    Nedwin GE, Jarrett-Nedwin J, Smith D et al. Structure and chromosomal localization of the human lymphotoxin gene. J Cell Biochem 1985; 29: 171–82.PubMedGoogle Scholar
  205. 204.
    Nedwin GE, Naylor SL, Sakaguchi AY et al. Human lymphotoxin and tumor necrosis factor genes: structure, homology and chromosomal localization. Nucl Acids Res 1985; 13: 6361–71.PubMedGoogle Scholar
  206. 205.
    Nelms K, Keegan AD, Zamorano J, Ryan JJ, Paul WE. The IL-4 receptor: signaling mechanisms and biologic functions. Annu Rev Immunol 1999; 17: 701–38.PubMedGoogle Scholar
  207. 206.
    Nemunaitis J, Rabinowe SN, Singer JW et al. Recombinant granulocyte-macrophage colony stimulating factor after autologous bone marrow transplantation for lymphoid cancer. N Engl J Med 1991; 324: 1773–8.PubMedGoogle Scholar
  208. 207.
    Niskanen E. Hematopoietic growth factors in clinical hematology. Ann Med 1991; 23: 615–24.PubMedGoogle Scholar
  209. 208.
    Novick D, Cohen B, Rubinstein M. Soluble interferon-alpha receptor molecules are present in body fluids. FEBS Lett 1993; 314: 445–8.Google Scholar
  210. 209.
    Novick D, Engelmann H Rubinstein M, Wallach D. Soluble cytokine receptors are present in normal human urine. J Exp Med 1989; 170: 1409–14.PubMedGoogle Scholar
  211. 210.
    Obreg K, Norheim I, Lind E. Treatment of malignant carcinoid tumors with human leukocyte interferon: long term results. Cancer Treat Rev 1986; 70: 1297–304.Google Scholar
  212. 211.
    Oehm A, Behrmann I, Falk W et al. Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumor necrosis factor/nerve growth factor receptor superfamily; sequence identity with the Fas antigen. J Biol Chem 1992; 267: 10932–7.Google Scholar
  213. Oppmann B, Lesley R, Blom B, Timans JC et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 2000; 13: 715–25.Google Scholar
  214. 214.
    Ostade XV, Vandenabeele P, Everaerdt B et al. Human TNF mutants with selective activity on the p55 receptor. Nature 1993; 361: 266–9.PubMedGoogle Scholar
  215. 215.
    Ostrand-Rosenberg S. Tumor immunotherapy: the tumor cell as an antigen-presenting cell. Curr Opin Immunol 1994; 6: 722–7.PubMedGoogle Scholar
  216. 216.
    Pardoll D. Cancer vaccines. Immunol Today 1993; 14: 310–16.PubMedGoogle Scholar
  217. 217.
    Parrish-Novak J, Dillon SR, Nelson A et al. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature 2000; 408: 57–63.PubMedGoogle Scholar
  218. 218.
    Park JW, Kirpotin DB, Hong K et al. Tumor targeting using anti her2 immunoliposomes. J Cont Release 2001; 74: 95–113.Google Scholar
  219. 219.
    Park CC, Morel JCM, Amin MA, Connors MA, Harlow LA, Koch AE. Evidence of IL-18 as a novel angiogenic mediator. J Immunol 2001; 167: 1644–53.PubMedGoogle Scholar
  220. 220.
    Pastan I, FitzGerald DJ. Recombinant toxins for cancer treatment. Science 1991; 254: 1173–7.PubMedGoogle Scholar
  221. 221.
    Pastan I, Chaudhary V, FitzGerald DJ. Recombinant toxins as novel therapeutic agents. Annu Rev Biochem 1992; 61: 331–54.PubMedGoogle Scholar
  222. 222.
    Paul SR, Bennet F, Calvetti JA 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: 7512–16.PubMedGoogle Scholar
  223. 223.
    Pennica D, Nedwin GE, Hayflick JS et al. Human tumor necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature 1984; 312: 724–9.PubMedGoogle Scholar
  224. 224.
    Peoples GE, Goedegebuure PS, Smith R, Linehen DC, Yoshino I, Eberlein TJ. Breast and ovarian cancer-specific cytotoxic T lymphocytes recognize the same HER1/neuderived peptide. Proc Natl Acad Sci USA 1995; 92: 432–6.PubMedGoogle Scholar
  225. 225.
    Pestka S. The human interferons–from protein purification and sequence to cloning and expression in bacteria: before, between and beyond. Arch Biochem Biophys 1983; 221: 1–37.PubMedGoogle Scholar
  226. 226.
    Pestka S. The purification and manufacture of human interferons. Sci Am 1983; 249: 36–43.Google Scholar
  227. 227.
    Pestka S, Langer JA, Zoom KC, Samuel CE. Interferons and their actions. Annu Rev Biochem 1987; 56: 727–77.PubMedGoogle Scholar
  228. 228.
    Petch L, Harris J, Raymond VW, Blasband A, Lee DC, Earp HS. A truncated secreted form of the epidermal growth factor receptor is encoded by an alternatively spliced transcript in normal rat tissue. Mol Cell Biol 1990; 10: 2973–82.PubMedCentralPubMedGoogle Scholar
  229. 229.
    Peters K, Vejlsgaard GL. Basal cell and squamous cell carcinoma and Kaposi’s carcinoma. Curr Opin Oncol 1992; 4: 380–5.PubMedGoogle Scholar
  230. 230.
    Petersen BH, DeHerdt SV, Schneck DW, Bumol TF. The human immune response eto KS1/4-desacetylvinblastin (LY256787) and KS1/4-desacetylvinblastin hydrazide (LY203728) in single and multiple dose clinical studies. Cancer Res 1991; 51: 2286–90.PubMedGoogle Scholar
  231. 231.
    Pietersz GA, McKenzie IFC. Antibody conjugates for the treatment of cancer. Immunol Rev 1992; 129: 57–80.PubMedGoogle Scholar
  232. 232.
    Plautz GE, Yang ZY, Wu BY, Gao X, Huang L, Nabel GJ. Immunotherapy of malignancy by in vivo gene transfer into tumors. Proc Natl Acad Sci USA 1993; 10: 4645–9.Google Scholar
  233. 233.
    Pluckthun A. Antibodies from Escherichia coli. Nature 1990; 347: 497–8.PubMedGoogle Scholar
  234. 234.
    Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B. A model for p53-induced apoptosis. Nature 1997; 389: 300–5.PubMedGoogle Scholar
  235. 235.
    Porgador A, Tzehoval E, Katz A et al. Interleukin 6 gene transfection into Lewis lung carcinoma tumor cells suppresses the malignant phenotype and confers immunotherapeutic competence against parental metastatic cell. Cancer Res 1992; 52: 3679–86.PubMedGoogle Scholar
  236. 236.
    Press OW, Eary JF, Appelbaum FR et al. Radiolabeled antibody therapy of B cell lymphoma with autologous bone marrow support. N Engl J Med 1993; 329: 1219–24.PubMedGoogle Scholar
  237. 237.
    Quesada JR, Hersh E.M, Manning J et al. Treatment of hairy cell leukemia with recombinant a-interferon. Blood 1986; 68: 493–7.PubMedGoogle Scholar
  238. 238.
    Ramakrishnam S, Bjorn MJ, Houston LL. Recombinant ricin A chain conjugated to monoclonal antibodies: improved tumor cell inhibition in the presence of lysosomotropic compounds. Cancer Res 1989; 49: 613–17.Google Scholar
  239. 239.
    Renauld JC, Druez C, Kermouni A et al. Expression cloning of the murine and human interleukin 9 receptor cDNAs. Proc Natl Acad Sci USA 1992; 89: 5690–4.PubMedGoogle Scholar
  240. 240.
    Renauld JC, Houssiau F, Louahed J, Vink A, Van Snick J, Uyttenhove C. Interleukin-9. Adv Immunol 1993; 54: 79–97.PubMedGoogle Scholar
  241. 241.
    Rinderknecht E, O’Connor BH, Rodriguez H. Natural human interferon gamma. J Biol Chem 1984; 259: 6790–7.PubMedGoogle Scholar
  242. 242.
    Rosenberg SA. Immunotherapy and gene therapy of cancer. Cancer Res 1991; 51: 5074s - 9s.PubMedGoogle Scholar
  243. 243.
    Rosenberg SA, Lotze MT, Muul LM et al. Observations on the systemic administration of autologous lymphokine activated killer cells and recombinant interleukin-2 of high dose IL-2 alone. N Engl J Med 1985; 313: 1485–90.PubMedGoogle Scholar
  244. 244.
    Rosenberg SA, Lotze MT, Yang JC et al. Combination therapy with interleukin-2 and alpha-interferon for treatment of patients with advanced cancer. J Clin Oncol 1989; 7: 1863–74.PubMedGoogle Scholar
  245. 245.
    Rosenberg SA, Spiess P, Lafreniere RA. A new approach to the adoptive immunotherapy of cancer with tumor infiltrating lymphocytes. Science 1986; 233: 1318–21.PubMedGoogle Scholar
  246. 246.
    Rosenblum RG, Unger BW, Gutterman JU, Hersh EM, David GS, Frincke JM. Modification of human leukocyte interferon pharmacology with a monoclonal antibody. Cancer Res 1985; 45: 2421–4.PubMedGoogle Scholar
  247. 247.
    Ross C, Tingsgaard P, Jorgensen H, Vejlsgaard GL. Interferon treatment of cutaneous T-cell lymphoma. Eur J Haematol 1993; 51: 63–72.PubMedGoogle Scholar
  248. 248.
    Samakrishnan S, Bjorn MJ, Houston LL. Recombinant ricin A chain conjugated to monoclonal antibodies: improved tumor cell inhibition in the presence of lysosomotropic compounds. Cancer Res 1989; 49: 613–17.Google Scholar
  249. 249.
    Sambrook J, Fritsch EF, Manatis T. Molecular Cloning: A Laboratory Manual. New York: Cold Spring Harbor Laboratory Press, 1989: 5. 30–5. 90.Google Scholar
  250. 250.
    Sanderson CJ. The biological role of interleukin-5. Int J Cell Cloning 1990; 8 (Suppl.1): 147–53.PubMedGoogle Scholar
  251. 251.
    Sasaki K, Chiba S, Mano H, Yazaki Y, Hirai H. Identification of a soluble GM-CSF binding-protein in the supernatant of a human choriocarcinoma cell line. Biochem Biophys Res Commun 1992; 183: 252–7.PubMedGoogle Scholar
  252. 252.
    Scambia G, Panici PB, Battaglia F et al. Receptors for epidermal growth factor and steroid hormones in primary lyrangeal tumors. Cancer 1991; 67: 1347–51.PubMedGoogle Scholar
  253. 253.
    Sceinberg DA, Straus DJ, Yeh SD et al. A phase I toxicity, pharmacology, and dosimetery trial of monoclonal antibody OKB7 in patients with non-Hodgkin’s lymphoma: effect of tumor burden and antigen expression. J Clin Oncol 1990; 8: 792–803.Google Scholar
  254. 254.
    Scherf U, Ross DT, Waltham M. A gene expression database for the molecular pharmacology of cancer. Nat Genet 2000; 24: 236–44.PubMedGoogle Scholar
  255. 255.
    Shaffer AL, Rosenwald A, Hurt EM et al. Signatures of the immune response. Immunity 2001; 15: 375–85.PubMedGoogle Scholar
  256. 256.
    Sherlock G, Hernandez-Boussard T, Kasarskis A et al. The Stanford Microarray Database. Nucleic Acids Res 2001; 29: 152–5.PubMedCentralPubMedGoogle Scholar
  257. 257.
    Schiro R, Longoni D, Rossi V et al. Suppression of juvenile chronic myelogenous leukemia colony growth by IL-1 receptor antagonist. Blood 1994; 83: 460–5.PubMedGoogle Scholar
  258. 258.
    Seigall CB, Xu YH, Cahudary VK, Adhya S, Fitzgerald D, Pastan I. Cytotoxic activities of a fusion protein compromised of TGFa and Pseudomonas exotoxin FASEB J 1989; 3: 2647–52.Google Scholar
  259. 259.
    Sen GC, Lengyel P. The interferon system. J Biol Chem 1992; 267: 5017–20.PubMedGoogle Scholar
  260. 260.
    Sharma S, Mehta S, Morgan J, Maizel A. Molecular cloning and expression of a human B-cell growth factor gene in E. coli. Science 1985; 235: 1489–92.Google Scholar
  261. 261.
    Shoyab M, Plowman GD, McDonald VL, Bradley JG, Todaro GJ. Structure and function of human amphiregulin: a member of the epidermal growth factor family. Science 1989; 243: 1074–6.PubMedGoogle Scholar
  262. 262.
    Sica GL, Zhu G, Tamada K, Liu D, Ni J, Chen L. RELT, a new member of the tumor necrosis factor receptor super-family, is selectively expressed in hematopoietic tissues and activates transcription factor NF-kappaB. Blood 2001; 97: 2702–7.PubMedGoogle Scholar
  263. 263.
    Siegall CB, FitzGerald DJ, Pastan I. Cytotoxicity of IL6- PE40 and derivatives on tumor cells expressing a range of interleukin 6 receptor levels. J Biol Chem 1990; 265: 16318–23.PubMedGoogle Scholar
  264. 264.
    Siegall CB, FitzGerald DJ, Pastan I. Selective killing of IL6 receptor bearing myeloma cells using recombinant IL6- Pseudomonas toxin. Curr Top Microbiol Immunol 1990; 166: 63–9.PubMedGoogle Scholar
  265. 265.
    Siegall CB, Kreitman RJ, FitzGerald DJ, Pastan I. Antitumor effects of interleukin-6 Pseudomonas exotoxin chimeric molecules against the human hepatocellular carcinoma. Cancer Res 1991; 51: 2831–6.PubMedGoogle Scholar
  266. 266.
    Sievers EL, Appelbaum FR, Spielberger RT et al. Selective ablation of acute myeloid leukemia using antibody-targeted chemotherapy: a phase I study of an anti-CD33 calicheamicin immunoconjugate. Blood 1999; 93: 3678–84.PubMedGoogle Scholar
  267. 267.
    Sims JE, Acres RB, Grubin CE et al. Cloning of the interleukin-1 receptor from human T-cells. Proc Natl Acad Sci USA 1989; 86: 8946–50.PubMedGoogle Scholar
  268. 268.
    Sims JE, March CJ, Cosman D et al. cDNA expression cloning of the IL-1 receptor, a member of the immunoglobulin superfamily. Science 1988; 241: 585–9.Google Scholar
  269. 269.
    Singh A, Ni J, Aggarwal BB. Death domain receptors and their role in cell demise. J Interferon Cytokine Res 1998; 18: 439–50.PubMedGoogle Scholar
  270. 270.
    Skolnick AA. First immunotoxin therapy for many common solid tumors enters phase I clinical trial. J Am Med Assoc 1993; 270: 2280.Google Scholar
  271. 271.
    Slamon D, Leyland-Jones B, Shak S et al. Use of chemotherapy plus a monoclonal antibody against HER-2 for metastatic breast cancer that overexpresses HER-2. N Engl J Med 2001; 344: 783–92.PubMedGoogle Scholar
  272. 272.
    Smalley RV, Andersen JW, Hawkins MJ et al. Interferon alpha combined with cytotoxic chemotherapy for patients with non-Hodgkin’s lymphoma. N Engl J Med 1992; 327: 1336–41.PubMedGoogle Scholar
  273. 273.
    Smith CM. Bioinformatics, genomics, and proteomics. Scientist 2000; 14: 26–8.Google Scholar
  274. 274.
    Smith CA, Davis T, Anderson D et al. A receptor for human tumor necrosis factor defines an unusual family of cellular and viral proteins. Science 1990; 248: 1019–23.PubMedGoogle Scholar
  275. 275.
    Solal-Celigny P, Lepage E, Brousse N et al. Recombinant interferon alfa-2b combined with a regimen containing doxorubicin in patients with advanced follicular lymphoma. N Engl J Med 1993; 329: 1608–14.PubMedGoogle Scholar
  276. 276.
    Souza LM, Boone TC, Gabrilove J et al. Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. Science 1986; 232: 61–5.PubMedGoogle Scholar
  277. 277.
    Spencer VA, Davie JR. Signal transduction pathways and chromatin structure in cancer cells. J Cell Biochem (Suppl.) 2000; 27–35.Google Scholar
  278. 278.
    Spitler LE. Cancer vaccines: the interferon analogy (editorial). Cancer Biother 1995; 10: 1–3.PubMedGoogle Scholar
  279. 279.
    Spriggs MK, Hruby DE, Maliszewski CR et al. Vaccinia and cowpox viruses encode a novel secreted interleukin-1 binding protein. Cell 1992; 71: 145–52.PubMedGoogle Scholar
  280. 280.
    Stebbing N, Weck PK. Preclinical assessment of biological properties of recombinant DNA derived interferons. In: Bollon AP, ed. Recombinant DNA Products: Insulin, Interferon, and Growth Hormone. Boca Raton, FL: CRC Press, 1984: 75–114.Google Scholar
  281. 281.
    Stills HF, Bullock BC, Clarkson TB. Increased atherosclerosis and glomerulonephritis in cynomolgus monkeys given injections of BSA over an extended period of time. J Pathol 1983; 113: 222–34.Google Scholar
  282. 282.
    Strander H. Interferon treatment of human neoplasia. Adv Cancer Res 1986; 46: 1–265.PubMedGoogle Scholar
  283. 283.
    Strander H, Cantell K, Jakobsson PA, Nilsonn U, Soderberg G. Exogenous interferon therapy of osteogenic sarcoma. Oerhop Scand 1975; 45: 958–9.Google Scholar
  284. 284.
    Strom TB, Anderson PL, Rubin-Kelley VE, Williams DP, Kijokawa T, Murphy JR. Immunotoxins and cytotokine toxin fusion proteins. Semin Immunol 1990; 2: 467–79.PubMedGoogle Scholar
  285. 285.
    Su AI, Welsh JB, Sapinoso LM et al. Molecular classification of human carcinomas by use of gene expression signatures. Cancer Res 2001; 61: 7388–93.PubMedGoogle Scholar
  286. 286.
    Suda T, Takahashi T, Golstein P, Nagata S. Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell 1993; 75: 1169–78.PubMedGoogle Scholar
  287. 287.
    Suzuki H, Yasukawa K, Saito T et al. Anti-human IL-6 receptor antibody inhibits human myeloma growth in vivo. Eur J Immunol 1992; 22: 1189–93.Google Scholar
  288. 288.
    Takatsu K. Interleukin 5 and B cell differentiation Cytokine Growth Factor Rev 1998; 9: 25–35.Google Scholar
  289. 289.
    Takaki S, Tominaga A, Hitoshi Y et al. Molecular cloning and expression of the murine interleukin-5 receptor. EMBO J 1990; 9: 4367–74.PubMedGoogle Scholar
  290. 290.
    Talpaz M, Kantarjian HM, McCredie K, Trujillo JM, Keating MJ, Gutterman JU. Hematological remission and cytogenetic improvement induced by recombinant human interferon alpha in chronic myelogenous leukemia. N Engl J Med 1986; 314: 1065–9.PubMedGoogle Scholar
  291. 291.
    Talpaz M, O’Brien S, Rose E et al. Phase 1 study of polyethylene glycol formulation of interferon alpha-2B (Schering 54031) in Philadelphia chromosome positive chronic myelogenous leukemia. Blood 2001; 98: 1708–13.PubMedGoogle Scholar
  292. 292.
    Talapatra S, Thompson CB. Growth factor signaling in cell survival: implications for cancer treatment. J Pharmacol Exp Ther 2001; 298: 873–8.PubMedGoogle Scholar
  293. 293.
    Tanaguchi T, Ohno S, Fujii-KuriyamaY, Murmatsu M. The nucleotide sequence of human fibroblast interferon cDNA. Gene 1980; 10: 11–15.Google Scholar
  294. 294.
    Tanaka H, Satake IR, Ishikawa M, Matsuki S, Asano K. Pharmacokinetics of recombinant human granulocyte colony stimulating factor conjugated to polyethylene glycol in rats. Cancer Res 1991; 51: 3710–14.PubMedGoogle Scholar
  295. 295.
    Tao MH, Levy R. Idiotype/granulocyte-macrophage colony stimulating factor fusion protein as a vaccine for a B-cell lymphoma. Nature 1993; 362: 755–8.PubMedGoogle Scholar
  296. 296.
    Tartaglia LA, Goeddel DV. Two TNF receptors. Immunol Today 1992; 13: 151–3.PubMedGoogle Scholar
  297. 297.
    TeVelde AA, Huijbens RJF, DeVries JE, Figdor CG. Interleukin 4 inhibits secretion of IL-1, tumor necrosis factor and IL-6 by human monocytes. Blood 1990; 76: 1392–8.Google Scholar
  298. 298.
    The International Chronic Granulomatous Disease Comparative Study Group. N Engl J Med 1991; 324: 509–16.Google Scholar
  299. 299.
    Tiesman J, Hart CE. Identification of a soluble receptor for platelet-derived growth factor in cell-conditioned medium and human plasma. J Biol Chem 1993; 268: 9621–8.PubMedGoogle Scholar
  300. 300.
    Tong J, Gordon MS, Srour EF et al. In vivo administration of recombinant human stem cell factor expands the number of hematopoietic stem cells. Blood 1993; 82: 784–91.PubMedGoogle Scholar
  301. 301.
    Trail PA, Willner D, Lasch SJ et al. Cure of xenografted human carcinomas by BR96-doxorubicin conjugates. Science 1993; 261: 212–14.PubMedGoogle Scholar
  302. 302.
    Trauth BC, Klas C, Peters AMJ et al. Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science 1989; 245: 301–5.PubMedGoogle Scholar
  303. 303.
    Trillet-Lenoir V, Green J, Manegold C et al. Recombinant granulocyte colony stimulating factor reduces the infectious complications of cytotoxic chemotherapy. Eur J Cancer 1993; 29A: 319–24.Google Scholar
  304. 304.
    Trinchieri G. Interleukin-12 and its role in generation of Th1 cells. Immunol Today 1993; 14: 335–8.PubMedGoogle Scholar
  305. 305.
    Truitt GA, Brunda MJ, Levitt D, Anderson TD, Sherman MI. The therapeutic activity in cancer of interleukin-2 in combination with other cytokines. Current Surveys 1989; 8: 875–89.Google Scholar
  306. 306.
    Uckun FM, Evans WE, Forsyth CJ et al. Biotherapy of B-cell precursor leukemia by targeting Geninstein to CD19- associated tyrosine kinases. Science 1995; 267: 886–91.PubMedGoogle Scholar
  307. 307.
    Uckun FM, Frankel A. The current status of immunotoxins: an overview of experimental and clinical studies as presented at the 3rd International Symposium on Immunotoxicins. Leukemia 1993; 7: 341–8.PubMedGoogle Scholar
  308. 308.
    Upton C, Mossman K, McFadden G. Encoding of a homolog of the IFN-y amma receptor by myxoma virus. Science 1992; 258: 1369–72.PubMedGoogle Scholar
  309. 309.
    Ushio S, Namba M, Okura T et al. Cloning of the cDNA for human IFN-y amma-inducing factor, expression in Escherichia coli, and studies on the biologic activities of the protein. J Immunol 1996; 156: 4274–9.PubMedGoogle Scholar
  310. 310.
    Vadhan-Raj S, Kudelka AP, Garrison L et al. Effect of interleukin-1 on carboplatin-induced thrombocytopenia in patients with recurrent ovarian cancer. J Clin Oncol 1994; 12: 707–14.PubMedGoogle Scholar
  311. 311.
    Vadhan-Raj S, Papadopoulous NE, Burgess MA et al. Effects of PIXY321, a GM-CSF/IL-3 fusion protein, on chemotherapy-induced multilineage myelosuppression in patients with sarcoma. J Clin Oncol 1994; 12: 715–24.PubMedGoogle Scholar
  312. 312.
    Vadhan-Raj S. PIXY321 (GM-CSF/IL-3 fusion protein) biology and early clinical development. Stem Cells 1994; 12: 253–61.PubMedGoogle Scholar
  313. 313.
    Valezuela P, Medina A, Rutter WJ, Ammerer G, Hall BD. Synthesis and assembly of hepatitis B virus surface antigen particles in yeast. Nature 1982; 298: 347–50.Google Scholar
  314. 314.
    Vallera DA. Immunotoxicins: will their clinical promise be fulfilled? Blood 1994; 83: 309–14.PubMedGoogle Scholar
  315. 315.
    Van Der Bruggen P, Traversari C, Chomez P et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 1991; 254: 1643–7.PubMedGoogle Scholar
  316. 316.
    Velculescu VE, Madden SL, Zhang L et al. Analysis of human transcriptomes. Nat Genet 1999; 23: 387–8.PubMedGoogle Scholar
  317. Vieira P, deWaal Malefyt R, Dang W et al. Isolation and expression of human cytokine synthesis inhibitory factor (CSIF/IL-10) cDNA clones: homology to Epstein Barr virus open reading frame BCRF1. Proc Natl Acad Sci USA 1991; 88: 1172–6.Google Scholar
  318. 319.
    Vitetta ES, Thrope PE, Uhr JW. Immunotoxicins: magic bullets or misguided missiles. Immunol Today 1993; 14: 252–9.PubMedGoogle Scholar
  319. 320.
    Vitetta ES, Uhr JW. Monoclonal antibodies as agonists: an expanded role for their use in cancer therapy. Cancer Res 1994; 54: 5301–9.PubMedGoogle Scholar
  320. 321.
    Waldmann TA, Goldman CK, Bongiovanni KF et al. Therapy of patients with human T-cell lymphotropic virus I-induced adult T cell leukemia with anti -Tac, a monoclonal antibody to the receptor for interleukin- Blood 1988; 72: 1805–16.Google Scholar
  321. 322.
    Waldmann T, Tagaya Y, Bamford R. Interleukin-2, interleukin-15, and their receptors. Int Rev Immunol 1998; 16: 205–26.PubMedGoogle Scholar
  322. 323.
    Wang H, Marsters SA, Baker T et al. TACI-ligand interactions are required for T cell activation and collagen-induced arthritis in mice. Nat Immunol 2001; 2: 632–7.PubMedGoogle Scholar
  323. 324.
    Watson J (ed.). Recombinant DNA in Medicine and Industry. New York: WH Freeman, 1992: 453–71.Google Scholar
  324. 325.
    Weber J, Yang JC, Topalian SL et al. Phase I trial of subcutaneous interleukin-6 in patients with advance malignancies. J Clin Oncol 1993; 11: 499–506.PubMedGoogle Scholar
  325. 326.
    Welsh JB, Sapinoso LM, Su AI et al. Analysis of gene expression identifies candidate markers and pharmacological targets in prostate cancer. Cancer Res 2001; 61: 5974–8.PubMedGoogle Scholar
  326. 327.
    Welsh JB, Zarrinkar PP, Sapinoso S et al. Analysis of gene expression profiles in normal and neoplastic ovarian tissue samples identifies candidate molecular markers of epithelial ovarian cancer. Proc Natl Acad Sci USA 2001; 98: 1176–81.PubMedGoogle Scholar
  327. 328.
    Wetzel R, Heyneker HL, Goeddel DV et al. Production of biologically active N-desacetylthymosin in E. coli through expression of a chemically synthesized gene. Biochemistry 1980; 19: 6096–104.Google Scholar
  328. 329.
    Whetton AD. The biology and clinical potential of growth factors that regulate myeloid cell production. Trends Pharmacol Sci 1990; 11: 285–9.PubMedGoogle Scholar
  329. 330.
    Williams DE, Dunn JT, Park LS et al. GM-CSF/IL-3 fusion protein promotes neutrophil and platelet recovery in sub-lethally irradiated rhesus monkeys. Biotechnol Ther 1993; 4: 17–29.PubMedGoogle Scholar
  330. 331.
    Williams DE, Eisenman J, Baird A et al. Identification of a ligand for the c-kit protooncogene. Cell 1990; 63: 167–74.PubMedGoogle Scholar
  331. 332.
    Williams GT, Smith CA, Spooncer E, Dexter TM, Taylor DR. Hematopoietic colony stimulating factors promote cell survival by suppressing apoptosis. Nature 1990; 343: 76–9.PubMedGoogle Scholar
  332. 333.
    Winter G, Milstein C. Man-made antibodies. Nature 1991; 349: 293–9.PubMedGoogle Scholar
  333. 334.
    Wong GG, Witek J, Temple PA et al. Human GM-CSF: molecular cloning and the complementary DNA and purification of the natural and recombinant proteins. Science 1985; 228: 810–15.PubMedGoogle Scholar
  334. 335.
    Xie MH, Aggarwal S, Ho WH et al. Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2–4 and IL-22R. J Biol Chem 2000; 275: 31335–9.PubMedGoogle Scholar
  335. 336.
    Xu F, Lupu R, Rodriguez GC et al. Antibody induced growth inhibition is mediated through immunologically and functionally distinct epitopes on the extracellular domain of the erb B-2R gene product p185. Int J Cancer 1993; 53: 401–8.PubMedGoogle Scholar
  336. 337.
    Xu W, Presnell SR, Parrish-Novak J, Kindsvogel W et al. A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist. Proc Natl Acad Sci USA 2001; 98: 9511–16.PubMedGoogle Scholar
  337. 338.
    Yan M, Marsters SA, Grewal IS, Wang H, Ashkenazi A, Dixit VM. Identification of a receptor for BLyS demonstrates a crucial role in humoral immunity. Nat Immunol 2000; 1: 37–41.PubMedGoogle Scholar
  338. 339.
    Yan M, Wang H, Chan B et al. Activation and accumulation of B cells in TACI-deficient mice. Nat Immunol 2001; 2: 638–43.PubMedGoogle Scholar
  339. 340.
    Yang YC, Ciarletta AB, Temple PA et al. Human IL-3 (multi-CSF): identification by expression cloning of a novel hematopoietic growth factor related to human IL-3. Cell 1986; 47: 3–10.PubMedGoogle Scholar
  340. 341.
    Yanuck M, Carbone DP, Pendleton CD et al. A mutant p53 tumor suppressor protein is a target for peptide-induced CD8+ cytotoxic T cells. Cancer Res 1993; 53: 3257–61.PubMedGoogle Scholar
  341. 342.
    Yin M, Gopal V, Banavali S, Gartside P, Preisler H. Effects of IL-1 receptor antagonist on acute myeloid leukemia. Leukemia 1992; 6: 898–901.PubMedGoogle Scholar
  342. 343.
    Young DC, Wagner K, Griffin JD. Constitutive expression of the granulocyte macrophage colony stimulating factor gene in acute myeloblastic leukemia. J Clin Invest 1987; 79: 100–6.PubMedCentralPubMedGoogle Scholar
  343. 344.
    Yu J, Zhang L, Hwang PM, Rago C, Kinzler KW, Vogelstein B. Identification and classification of p53-regulated genes. Proc Natl Acad Sci USA 1999; 96: 14517–22.PubMedGoogle Scholar
  344. 345.
    Zhu N, Leggitt D, Liu Y, Debs R. Systemic gene expression after intravenous DNA delivery into adult mice. Science 1993; 261: 209–11.PubMedGoogle Scholar
  345. 346.
    Zurawski G, de Vries JE. Interleukin 13, an interleukin 4- like cytokine that acts on monocytes and B cells, but not on T cells. Immunol Today 1994; 15: 19–26.PubMedGoogle Scholar
  346. 347.
    Zwick E, Bange J, Ullrich A. Receptor tyrosine kinase signalling as a target for cancer intervention strategies. Endocr Relat Cancer 2001; 8: 161–73.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2003

Authors and Affiliations

  • Kapil Mehta
  • Kishor Gohil
  • Bharat B. Aggarwal

There are no affiliations available

Personalised recommendations