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Expert Opinion on Investigational Drugs Volume 14, 2005 - Issue 6
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Review

TGF-β inhibitors for the treatment of cancer

Michael Lahn Eli Lilly & Company Research Laboratories, Therapeutic Area Oncology, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. [email protected]
,
Susanne Kloeker Eli Lilly & Company Research Laboratories, Therapeutic Area Oncology, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. [email protected]
&
Brandi S Berry Eli Lilly & Company Research Laboratories, Therapeutic Area Oncology, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. [email protected]
Pages 629-643 | Published online: 11 Jul 2005

Bibliography

  • ROBERTS AB, ANZANO MA, LAMB LC et al: Isolation from murine sarcoma cells of novel transforming growth factors potentiated by EGF. Nature (1982) 295:417–419.
  • ROBERTS AB, ANZANO MA, LAMB LC, SMITH JM, SPORN MB: New class of transforming growth factors potentiated by epidermal growth factor: isolation from non-neoplastic tissues. Proc. Nati Acad. Sci. USA (1981) 78:5339–5343.
  • •Original article describing the role of TGF-13.
  • DERYNCK R, JARRETT JA, CHEN EY et al.: Human transforming growth factor-I3 complementary DNA sequence and expression in normal and transformed cells. Nature (1985) 316:701–705.
  • WAKEFIELD LM, ROBERTS AB, ASSOIAN RK et al: Structure and function of transforming growth factor-13. Proc. West Pharmacol. Soc. (1986) 29:475–477.
  • SPORN MB, ROBERTS AB: Autocrine growth factors and cancer. Nature (1985) 313:745–747.
  • AKHURST RJ, FEE F, BALMAIN A: Localized production of TGF-13 mRNA in tumour promoter-stimulated mouse epidermis. Nature (1988) 331:363–365.
  • KEHRL JH, WAKEFIELD LM, ROBERTS AB et al.: Production of transforming growth factor-I3 by human T lymphocytes and its potential role in the regulation of T cell growth. I Exp. Med. (1986) 163:1037–1050.
  • ROOK AH, KEHRL JH, WAKEFIELD LM et al.: Effects of transforming growth factor-I3 on the functions of natural killer cells: depressed cytolytic activity and blunting of interferon responsiveness. Immunol. (1986) 136:3916–3920.
  • ROBERTS AB, SPORN MB, ASSOIAN RK et al: Transforming growth factor type-13: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc. Natl. Acad. ScL USA (1986) 83:4167–4171.
  • SEYEDIN SM, THOMPSON AY, BENTZ H et al: Cartilage-inducing factor-A. Apparent identity to transforming growth factor-beta. .1 Biol. Chem. (1986) 261:5693–5695.
  • ROBEY PG, YOUNG ME FLANDERS KC et al.: Osteoblasts synthesize and respond to transforming growth factor-type-13 (TGF-13) in vitro. J. Cell Biol. (1987) 105:457–463.
  • WAKEFIELD LM, ROBERTS AB: TGF-13 signaling: positive and negative effects on tumorigenesis. Curt: Opin. Genet. Dev. (2002) 12:22–29.
  • YINGLING JM, WANG XF, BASSING CH: Signaling by the transforming growth factor-I3 receptors. Biochim. Biophys. Acta (1995) 1242:115–136.
  • ••Comprehensive review on TGF-13 incancer.
  • SIEGEL PM, MASSAGUE J: Cytostatic and apoptotic actions of TGF-I3 in homeostasis and cancer. Nat. Rev Cancer (2003) 3:807–821.
  • DE CAESTECKER MP, PIEK E, ROBERTS AB: Role of transforming growth factor-I3 signaling in cancer. Natl. Cancer Inst. (2000) 92:1388–1402.
  • WAKEFIELD LM, PIEK E, BOTTINGER EP: TGF-13 signaling in mammary gland development and tumorigenesis. I Mammary Gland Biol. Neoplasia (2001) 6:67–82.
  • MASSAGUE J, BLAIN SW, LO RS: TGF-13 signaling in growth control, cancer, and heritable disorders. Cell (2000) 103:295–309.
  • OFT M, PELI J, RUDAZ C et al: TGF-131and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. Genes Dev. (1996) 10:2462–2477.
  • BHOWMICK NA, NEILSON EG, MOSES HL: Stromal fibroblasts in cancer initiation and progression. Nature (2004) 432:332–337.
  • MICKE P, OSTMAN A: Tumour-stroma interaction: cancer-associated fibroblasts as novel targets in anti-cancer therapy? Lung Cancer (2004) 45\(Suppl. 2):5l63-5l75.
  • DERYNCK R, AKHURST RJ, BALMAIN A: TGF-I3 signaling in tumor suppression and cancer progression. Nat. Genet. (2001) 29:117–129.
  • YIN JJ, SELANDER K, CHIRGWIN JM et al: TGF-13 signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development. J. Clia Invest. (1999) 103:197–206.
  • BRIDLE KR, CRAWFORD DH, POWELL LW, RAMM GA: Role of myofibroblasts in tumour encapsulation of hepatocellular carcinoma in haemochromatosis. Liver (2001) 21:96–104.
  • BERKING C, TAKEMOTO R, SCHAIDER H et al: Transforming growth factor-131 increases survival of human melanoma through stroma remodeling. Cancer Res. (2001) 61:8306–8316.
  • PERTOVAARA L, KAIPAINEN A, MUSTONEN T et al: Vascular endothelial growth factor is induced in response to transforming growth factor-I3 in fibroblastic and epithelial cells. Biol. Chem. (1994) 269:6271–6274.
  • SHIMO T, NAKANISHI T, NISHIDA T et al: Involvement of CTGF, a hypertrophic chondrocyte-specific gene product, in tumor angiogenesis. Oncology (2001) 61:315–322.
  • KANG Y, SIEGEL PM, SHU W et al: A multigenic program mediating breast cancer metastasis to bone. Cancer Cell (2003) 3:537–549.
  • KAKONEN SM, SELANDER KS, CHIRGWIN JM et al.: Transforming growth factor-I3 stimulates parathyroid hormone-related protein and osteolytic metastases via Smad and mitogen-activated protein kinase signaling pathways. J. Biol. Chem. (2002) 277:24571–24578.
  • GORELIK L, FLAVELL RA: Immune-mediated eradication of tumors through the blockade of transforming growth factor-I3 signaling in T cells. Nat. Med. (2001) 7:1118–1122.
  • ••The role of TGF-13 in cancerimmunosuppression.
  • IBELGAUFTS H: Horst Ibelgaufts COPE: Cytokine Online Pathfinder Encyclopaedia. (2004).
  • ••One of the best resources on cytokines.
  • KINGSLEY DM: The TGF-13 superfamily: new members, new receptors, and new genetic tests of function in different organisms. Genes Dev. (1994) 8:133–146.
  • DIJKHUIZEN T, MOLENAAR WM, HOEKSTRA HJ, WIERSEMA J, VAN DEN BERG E: Cytogenetic analysis of a case of myxoid liposarcoma with cartilaginous differentiation. Cancer Genet. Cytogenet. (1996) 92:141–143.
  • SHU XO, GAO YT, CAI Q et al: Genetic polymorphisms in the TGF-131 gene and breast cancer survival: a report from the Shanghai Breast Cancer Study. Cancer Res. (2004) 64:836–839.
  • McKEOWN DJ, BROWN DJ, KELLY A, WALLACE AM, McMILLAN DC: The relationship between circulating concentrations of C-reactive protein, inflammatory cytokines and cytokine receptors in patients with non-small-cell lung cancer. BE J. Cancer (2004) 91:1993–1995.
  • CHEN YG, HATA A, LO RS et al: Determinants of specificity in TGF-13 signal transduction. Genes Dev. (1998) 12:2144–2152.
  • PARK BJ, PARK JI, BYUN DS, PARK JH,CHI SG: Mitogenic conversion of transforming growth factor-01 effect by oncogenic Ha-Ras-induced activation of the mitogen-activated protein kinase signaling pathway in human prostate cancer. Cancer Res. (2000) 60:3031–3038.
  • JOHANSSON N, ALA-AHO R, UITTO V et al.: Expression of collagenase-3 (MMP-13) and collagenase-1 (MMP-1) by transformed keratinocytes is dependent on the activity of p38 mitogen-activated protein kinase. 1 Cell. Sci. (2000) 113\(Part 2):227–235.
  • BAKIN AV, RINEHART C, TOMLINSON AK, ARTEAGA CL: p38 mitogen-activated protein kinase is required for TGF-13-mediated fibroblastic transdifferentiation and cell migration. J. Cell. Sri. (2002) 115:3193–3206.
  • BAKIN AV, TOMLINSON AK, BHOWMICK NA, MOSES HL, ARTEAGA CL: Phosphatidylinositol 3-kinase function is required for transforming growth factor 0-mediated epithelial to mesenchymal transition and cell migration. J. Biol. Chem. (2000) 275:36803–36810.
  • BHOWMICK NA, GHIASSI M, BAKIN A et al: Transforming growth factor-01 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism. Mol Biol. Cell (2001) 12:27–36.
  • TAMM I, DORKEN B, HARTMANN G: Antisense therapy in oncology: new hope for an old idea? Lancet (2001) 358:489–497.
  • ••Excellent overview on ASOs in the clinic.
  • DVORCHIK BH: The disposition (ADME) of antisense oligonucleotides. Curr. Opin. Mol. Ther. (2000) 2:253–257.
  • HAU P, BOGDAHN U, STAUDER G, KUNST M, SCHLINGENSIEPEN K-H: A TGF-132 specific antisense oligonucleotide (AP-12009) as continuous intratumoral treatment of recurrent high-grade glioma patients. Armeim-Forsch. Drug Res. (2003) 53:464.
  • STAUDER G, HAU P, BOGDAHN U et al: A TGF-132 specific antisense oligonucleotide (AP-12009) as continuous intratumoral treatment of recurrent high-grade glioma patients: A clinical phase I/II extension study. 39th ASCO Annual Meeting, IL, USA (2003):436 (Abstract).
  • BOGDAHN U, HAU P, BRAWANSKI A et al: TGF-132 suppression by the antisense oligonucleotide AP-12009 as therapy for high-grade glioma: safety and efficacy results of Phase I/II clinical studies. Proceedings of the American Asociation of Cancer Research (2004):5239 (Abstract).
  • BOGDAHN U, HAU P, BRAWANSKI A et al: Specific therapy for high-grade glioma by convection-enhanced delivery of the TGF-132 specific antisense oligonucleotide AP-12009. 40th ASCO Annual Meeting. New Orleans, LA, USA. (2004):4514 (Asbtract).
  • STAUDER G, BISCHOF A, EGGER T et al: TGF-132 suppression by the antisense oligonucleotide AP-12009 as treatment for pancreatic cancer: Preclinical efficacy data. ASCO Annual Meeting Proceedings. July 15 (2004):4106 (Abstract).
  • SCHLINGENSIEPEN K-H, BISCHOF A, EGGER T et al: The TGF-131 antisense oligonucleotide AP-11014 for the treatment of non-small cell lung, colorectal and prostate cancer: preclinical studies. American Socieo, of Clinical Oncology Annual Meeting (2004):3132 (Abstract).
  • FAKHRAI H, DORIGO 0, SHAWLER DL et al.: Eradication of established intracranial rat gliomas by transforming growth factor-I3 antisense gene therapy. Proc. Natl. Acad. Li. USA (1996) 93:2909–2914.
  • BASELGA J, GIANNI L, GEYER C et al: Future options with trastuzumab for primary systemic and adjuvant therapy. Smith Oncol (2004) 31:51–57.
  • GATTO B: Monoclonal antibodies in cancer therapy. Curr. Med. Chem. Anti-Canc. Agents (2004) 4:411–414.
  • •Review on the development of monoclonal antibody therapy in oncology.
  • CHRISTIANSEN J, RAJASEKARAN AK: Biological impediments to monoclonal antibody-based cancer immunotherapy. Mol Cancer Ther. (2004) 3:1493–1501.
  • MEAD AL, WONG TT, CORDEIRO MF, ANDERSON IK, KHAW PT: Evaluation of anti-TGF-132 antibody as a new postoperative anti-scarring agent in glaucoma surgery. Invest. Ophthalmol Li. (2003) 44:3394–3401.
  • CORDEIRO MF: Technology evaluation: lerdelimumab, Cambridge Antibody Technology. Curr. Opin. Mol Ther. (2003) 5:199–203.
  • DASCH JR, PACE DR, WAEGELL W, INENAGA D,ELLINGS WORTH L: Monoclonal antibodies recognizing transforming growth factor-13. Bioactivity neutralization and transforming growth factor-132 affinity purification. J. Immunol (1989) 142:1536–1541.
  • NANDA S, BATHON JM: Etanercept: aclinical review of current and emerging indications. Expert Opia Pharmacother. (2004) 5:1175–1186.
  • YANG YA, DUKHANINA 0, TANG B et al.: Lifetime exposure to a soluble TGF-I3 antagonist protects mice against metastasis without adverse side effects. J. Clin. Invest. (2002) 109:1607–1615.
  • ROWLAND-GOLDSMITH MA, MARUYAMA H, MATSUDA K et al.: Soluble type II transforming growth factor-I3 receptor attenuates expression of metastasis-associated genes and suppresses pancreatic cancer cell metastasis. Mol. Cancer Ther. (2002) 1:161–167.
  • ROWLAND-GOLDSMITH MA, MARUYAMA H, KUSAMA T, RALLI S, KORC M: Soluble type II transforming growth factor-I3 (TGF-13) receptor inhibits TGF-I3 signaling in COLO-357 pancreatic cancer cells in vitro and attenuates tumor formation. Clin. Cancer Res. (2001) 7:2931–2940.
  • SAWYER JS, ANDERSON BD, BEIGHT DW et al.: Synthesis and activity of new aryl- and heteroaryl-substituted pyrazole inhibitors of the transforming growth factor-I3 type I receptor kinase domain. I Med. Chem. (2003) 46:3953–3956.
  • SAWYER JS, BEIGHT DW, BRITT KS et al.: Synthesis and activity of new aryl- and heteroaryl-substituted 5,6-dihydro-4H-pyrrolo(1,2-b)pyrazole inhibitors of the transforming growth factor-I3 type I receptor kinase domain. Bioorg. Med. Chem. Lett. (2004) 14:3581–3584.
  • YINGLING JM, BLANCHARD KL, SAWYER JS: Development of TGF-I3 signalling inhibitors for cancer therapy. Nat. Rev Drug Discov. (2004) 3:1011–1022.
  • GELLIBERT F, WOOLVEN J, FOUCHET MH et al.: Identification of 1,5-naphthyridine derivatives as a novel series of potent and selective TGF-I3 type I receptor inhibitors. J. Med. Chem. (2004) 47:4494–4506.
  • YINGLING JM, YAN L, PEERY RB et al.: Dihydropyrrolopyrazoles as TGF-I3 receptor kinase inhibitors for cancer therapy. 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Geneva, Switzerland (2004):318 (Abstract).
  • CALLAHAN JF, BURGESS JL, FORNWALD JA et al.: Identification of novel inhibitors of the transforming growth factor Pi (TGF-131) type 1 receptor (ALK5). J. Med. Chem. (2002) 45:999–1001.
  • INMAN GJ, NICOLAS FJ, CALLAHAN JF et al: SB-431542 is a potent and specific inhibitor of transforming growth factor-I3 superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Mol. Pharmacol. (2002) 62:65–74.
  • LAPING NJ, GRYGIELKO E, MATHUR A et al.: Inhibition of transforming growth factor (TGF)-131-induced extracellular matrix with a novel inhibitor of the TGF-I3 type I receptor kinase activity: SB-431542. Mol. Pharmacol. (2002) 62:58–64.
  • BYFIELD SD, ROBERTS AB: Lateral signaling enhances TGF-I3 response complexity. Trends Cell. Biol. (2004) 14:107–111.
  • BONNIAUD P, KOLB M, GALT T et al.:Smad3 null mice develop airspace enlargement and are resistant to TGF-131-mediated pulmonary fibrosis. J. Immunol. (2004) 173:2099–2108.
  • BONNIAUD P, MARGETTS PJ, KOLB M et al.: Progressive TGF-131-induced lung fibrosis is blocked by an orally active ALK5 kinase inhibitor. Am. .1 Respir. Grit. Care Med. (2004).
  • BONNIAUD P, MARTIN G, MARGETTS PJ et al.: Connective tissue growth factor is crucial to inducing a profibrotic environment in ''fibrosis-resistant'' BALB/c mouse lungs. Am. Respir. Cell Mol. Biol. (2004) 31:510–516.
  • UHL M, AULWURM S, WISCHHUSEN J et al.: SD-208, a novel transforming growth factor-I3 receptor I kinase inhibitor, inhibits growth and invasiveness and enhances immunogenicity of murine and human glioma cells in vitro and in vivo. Cancer Res. (2004) 64:7954–7961.
  • HAYASHI T, HIDESHIMA T, PODAR K et al.: TGF-I3 receptor I kinase inhibitor downregulates cytokine secretion and multiple myeloma cell growth in the bone marrow microenvironment. American Socieo, of Hematology, San Diego, USA, November 16 (2004):2355 (Abstract).
  • JOHNSON JI, DECKER S, ZAHAREVITZ D et al.: Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials. Br. J. Cancer (2001) 84:1424–1431.
  • ••Important review on testing compounds inearly drug development.
  • GITLER MS, SAUSVILLE EA, HOLLINGSHEAD M, SHOEMAKER R: In vivo models for experimental therapeutics relevant to human cancer. Cancer Res. (2004) 64:8478–8480.
  • CAPPUZZO F, MAGRINI E, CERESOLI GL et al.: Akt phosphorylation and gefitinib efficacy in patients with advanced non-small-cell lung cancer. J. Nati Cancer. Inst. (2004) 96:1133–1141.
  • KATTAN MW, SHARIAT SF, ANDREWS B et al.: The addition of interleukin-6 soluble receptor and transforming growth factor-131 improves a preoperative nomogram for predicting biochemical progression in patients with clinically localized prostate cancer. J. Clin. Oncol. (2003) 21:3573–3579.
  • •The role of TGF-13 as a predictor in prostate cancer.
  • SHARIAT SF, KATTAN MW, TRAXEL E et al.: Association of pre- and post-operative plasma levels of transforming growth factor-No and interleukin 6 and its soluble receptor with prostate cancer progression. Clin. Cancer Res. (2004) 10:1992–1999.
  • SHARIAT SF, KIM JH, ANDREWS B et al.: Preoperative plasma levels of transforming growth factor-NO strongly predict clinical outcome in patients with bladder carcinoma. Cancer (2001) 92:2985–2992.
  • SHARIAT SF, SHALEV M, MENESSES-DIAZ A et al.: Preoperative plasma levels of transforming growth factor-(TGF-13(1)) strongly predict progression in patients undergoing radical prostatectomy.Oncol. (2001)19:2856–2864.
  • WOLFF JM, FANDEL TH, BORCHERS H, JAKSE G: Serum concentrations of transforming growth factor-131 in patients with benign and malignant prostatic diseases. Anticancer Res. (1999) 19:2657–2659.
  • WOLFF JM, FANDEL T, BORCHERS H, BREHMER B Jr, JAKSE G: Transforming growth factor-131 serum concentration in patients with prostatic cancer and benign prostatic hyperplasia. BE J. Urol. (1998) 81:403–405.
  • SHULL MM, DOETSCHMAN T: Transforming growth factor-131 in reproduction and development. Mol. Reprod. Dev. (1994) 39:239–246.
  • SHULL MM, ORMSBY I, KIER AB et al.:Targeted disruption of the mouse transforming growth factor-131 gene results in multifocal inflammatory disease. Nature (1992) 359:693–699.
  • KULKARNI AB, HUH CG, BECKER D et al.: Transforming growth factor-131 null mutation in mice causes excessive inflammatory response and early death. Proc. Natl. Acad. Sci USA (1993) 90:770–774.
  • KALLAPUR S, ORMSBY I, DOETSCHMAN T: Strain dependency of TGF-131 function during embryogenesis. Mol Reprod Dev (1999) 52:341–349.
  • WAHL SM, ORENSTEIN JM, CHEN W: TGF-I3 influences the life and death decisions of T lymphocytes. Cytokine Growth Factor Rev. (2000) 11:71–79.
  • WILLIAMS AO, KNAPTON AD, GEISER A, LETTERIO JJ, ROBERTS AB: The liver in transforming growth factor-131 (TGF-131) null mutant mice. Ultrastruct. Pathol (1996) 20:477–490.
  • BOIVIN GP, O'TOOLE BA, ORSMBY IEet al: Onset and progression of pathological lesions in transforming growth factor-131-deficient mice. Am. J. Pathol (1995) 146:276–288.
  • KULKARNI AB, WARD JM, YASWEN L et al.: Transforming growth factor-131 null mice. An animal model for inflammatory disorders. Am. .1 Pathol. (1995) 146:264–275.
  • GORHAM JD, LIN JT, SUNG JL, RUDNER LA, FRENCH MA: Genetic regulation of autoimmune disease: BALB/c background TGF-131-deficient mice develop necroinflammatory IFN-y-dependent hepatitis. J. Immunol (2001) 166:6413–6422.
  • GORELIK L, FLAVELL RA: Abrogation ofTGF-I3 signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease. Immunity (2000) 12:171–181.
  • BOIVIN GP, ORMSBY I, JONES-CARSON J, O'TOOLE BA, DOETSCHMAN T: Germ-free and barrier-raised TGF-131-deficient mice have similar inflammatory lesions. Transgenic Res. (1997) 6:197–202.
  • LETTERIO JJ, GEISER AG, KULKARNI AB et al: Autoimmunity associated with TGF-131-deficiency in mice is dependent on MHC class II antigen expression. J. Clip. Invest. (1996) 98:2109–2119.
  • SANFORD LP, ORMSBY I, GITTENBERGER-DE GROOT AC et al: TGF-132 knockout mice have multiple developmental defects that are non-overlapping with other TGF-I3 knockout phenotypes. Development (1997) 124:2659–2670.
  • KAARTINEN V, VONCKEN JW, SHULER C et al.: Abnormal lung development and cleft palate in mice lacking TGF-133 indicates defects of epithelial-mesenchymal interaction. Nat. Genet. (1995) 11:415–421.
  • LARSSON J, GOUMANS MJ, SJOSTRAND LJ et al.: Abnormal angiogenesis but intact hematopoietic potential in TGF-I3 type I receptor-deficient mice. Embo. J. (2001) 20:1663–1673.
  • OSHIMA M, OSHIMA H, TAKETO MM: TGF-I3 receptor type II deficiency results in defects of yolk sac hematopoiesis and vasculogenesis. Dev. Biol. (1996) 179:297–302.
  • DICKSON MC, MARTIN JS, COUSINS FM et al.: Defective haematopoiesis and vasculogenesis in transforming growth factor-f31 knock out mice. Development (1995) 121: 1845-1854.
  • WEINSTEIN M, YANG X, DENG C: Functions of mammalian Smad genes as revealed by targeted gene disruption in mice. Cytokine Growth Factor Rev. (2000) 11:49–58.
  • NOMURA M, LIE: Smad2 role in mesoderm formation, left-right patterning and craniofacial development. Nature (1998) 393:786–790.
  • WEINSTEIN M, YANG X, LI C et al: Failure of egg cylinder elongation and mesoderm induction in mouse embryos lacking the tumor suppressor smad2. Proc. Nati Acad. Sci. USA (1998) 95:9378–9383.
  • WALDRIP WR, BIKOFF EK, HOODLESS PA, WRANA JL, ROBERTSON EJ: Smad2 signaling in extraembryonic tissues determines anterior-posterior polarity of the early mouse embryo. Cell (1998) 92:797–808.
  • DATTO M, WANG XF: The Smads: transcriptional regulation and mouse models. Cytokine Growth Factor Rev. (2000) 11:37–48.
  • ASHCROFT GS, YANG X, GLICK AB et al: Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response. Nat. Cell Biol. (1999) 1:260–266.
  • YANG X, LETTERIO JJ, LECHLEIDER RJ et al.: Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-13. Emba../. (1999) 18:1280–1291.
  • ZHU Y, RICHARDSON JA, PARADA LF, GRAFF JM: Smad3 mutant mice develop metastatic colorectal cancer. Cell (1998) 94:703–714.
  • YAO JY, WANG Y, AN J et al: Mutation analysis of the Smad3 gene in human osteoarthritis. Eur. J. Hum. Genet. (2003) 11:714–717.
  • UEBERHAM E, LOW R, UEBERHAM U et al.: Conditional tetracycline-regulated expression of TGF-131 in liver of transgenic mice leads to reversible intermediary fibrosis. Hepatology (2003) 37:1067–1078.
  • LEVEEN P, LARSSON J, EHINGER M et al.: Induced disruption of the transforming growth factor-I3 type II receptor gene in mice causes a lethal inflammatory disorder that is transplantable. Blood (2002) 100:560–568.
  • FRAZIER KS, NOLD JB, SCICCHITANO MS et al: Physeal hypertrophy is pharmacologic biomarker for transforming growth factor-I3 receptor inhibitory activity in rats. Combined 55th and 39th Annual Meetings of the American College of Veterinary Pathologists and the American Socieg, for Veterinary Clinical Pathology, FL, November 13-17 (2004):170 (Abstract).
  • CHEN W, WAHL SM: TGF-13: the missing link in CD4(÷)CD25(÷) regulatory T cell-mediated immunosuppression. Cytokine Growth Factor Rev. (2003) 14:85–89.
  • WOHLFERT EA, CALLAHAN MK, CLARK RB: Resistance to CD4*CD25' regulatory T cells and TGF-I3 in C bl -b mice. J. Immunol (2004) 173:1059–1065.
  • HEROLD KC, TAYLOR L: Treatment of type 1 diabetes with anti-CD3 monoclonal antibody: induction of immune regulation? Immunol. Res. (2003) 28:141–150.
  • HEROLD KC, BURTON JB, FRANCOIS F et al.: Activation of human T cells by FcR nonbinding anti-CD3 mAb, hOKT3y1(Ala-Ala) Clip. Invest. (2003) 111:409–418.
  • HEROLD KC, HAGOPIAN W, AUGER JA et al: Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl. J. Med. (2002) 346:1692–1698.
  • CHATENOUD L, SALOMON B, BLUESTONE JA: Suppressor T cells- they're back and critical for regulation of autoimmunityl brununol. Rev. (2001) 182:149–163.
  • ABRAMS SI: Role of anti-CTLA-4 therapies in the treatment of cancer. Curr. Opin. Mal. Then (2004) 6:71–77.
  • HODI FS, MIHM MC, SOIFFER RJ et al.: Biologic activity of cytotoxic T lymphocyte-associated antigen-4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc. Nati Acad. Sri. USA (2003) 100:4712–4717.
  • PHAN GQ, YANG JC, SHERRY RM et al.: Cancer regression and autoimmunity induced by cytotoxic T lymphocyte- associated antigen-4 blockade in patients with metastatic melanoma. Proc. Nati Acad. Sri. USA (2003) 100:8372–8377.
  • •Important study of immunosuppressive therapy in cancer patients.

Websites

  • http://www.antisense-pharma.com Antisense Pharma website.
  • http://www.novarx-pharma.com NovaRx Pharma website.
  • http://www.cambridgeantibody.com/html Cambridge Antibody Technology'.
  • http://www.cambridgeantibody.com/html/ investor_relations/reports_and_accounts 2004 interim results and annual report.
  • http://www.genzyme.com/corp/investors/ pipe_home.asp Genzyme corporate pipeline.
  • http://www.astrazeneca.com/pressrelease/ 4245.aspx Press release December 17 2004.

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