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Gen-Medizin pp 267-331 | Cite as

Therapie mit Genen: Erfahrungen und Zukunftsperspektiven 10 Jahre nach ihrer klinischen Einführung

  • S. Nikol
  • M. Hallek
Chapter
  • 105 Downloads

Zusammenfassung

Kaum ein anderes biomedizinisches Forschungsgebiet hat in den letzten Jahren so viel Aufmerksamkeit erregt wie die Gentherapie. Die Voraussetzungen für diese schnelle Entwicklung schufen die bahnbrechenden Entdeckungen der Molekularbiologen in der zweiten Hälfte dieses Jahrhunderts. Die von dem Nobelpreisträger Nirenberg 1967 geäußerte Prognose „My guess is that cells will be programmed with synthetic messages within 25 years“ hat sich erfüllt. Mit raffinierten Methoden gelingt es heute, Gene in Zellen einbringen und dadurch neu programmieren. In der Öffentlichkeit hat der Gentherapie-Boom zu einer hohen und manchmal unrealistischen Erwartungshaltung bei der Therapie von Patienten mit hohem Leidensdruck geführt, bei denen konventionelle Therapien bisher versagten. Nach der ersten therapeutischen Anwendung 1990, hat sich das große Potential der Gentherapie bestätigt, wenn auch der Weg zur routinemäßigen Anwendung länger als erwartet ist.

Literatur

  1. Aebischer P, Schluep M, Deglon N, Joseph JM, Hirt L, Heyd B, Goddard M, Hammang JP, Zurn AD, Kato AC, Regli F, Baetge EE (1996) Erratum: Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients (Nature Medicine (1996) Vol. 2 (pp. 696-699)). Nat Med 2(9): 1041CrossRefGoogle Scholar
  2. Albelda SM (1997) Gene therapy for lung cancer and mesothelioma. Chest 111(6 Suppl): 144S–149SPubMedCrossRefGoogle Scholar
  3. Barinaga M (1993) Ribozymes: killing the messenger. Science 262: 1512–1514.PubMedCrossRefGoogle Scholar
  4. Barnes MN, Deshane JS, Rosenfeld M, Siegal BG, Curiel DT, Alvarez RD (1997) Gene therapy and ovarian cancer: a review. Obstetrics and Gynecology 89(1): 145–155.PubMedCrossRefGoogle Scholar
  5. Baumgartner I, Pieczek A, Manor O, Blair R, Kearney M, Walsh K, Isner JM (1998) Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia. Circulation 97(12): 1114–1123PubMedCrossRefGoogle Scholar
  6. Belli F, Arienti F, Sulesuso J, Clemente C, Mascheroni L, Cattelan A, Sanantonio C, Gallino GF, Melani C, Rao S, Colombo MP, Maio M, Cascinelli N and Parmiani G (1997) Active immunization of metastatic melanoma patients with interleukin 2 transduced allogeneic melanoma cells: Evaluation of efficacy and tolerability. Cancer Immunol Immunother 44(4): 197–203.PubMedCrossRefGoogle Scholar
  7. Bellon G, Michelcalemard L, Thouvenot D, Jagneaux V, Poitevin F, Malcus C, Accart N, Layani MP, Aymard M, Bernon H, Bienvenu J, Courtney M, Doring G, Gilly B, Gilly R, Lamy D, Levrey H, Morel Y, Paulin C, Perraud F, Rodillon L, Sene C, So S, Tourainemoulin F, Schatz C, Pavirani A (1997) Aerosol administration of a recombinant adenovirus expressing CFTR to cystic fibrosis patients: a phase I clinical trial. Hum Gene Ther 8(1): 15–25.PubMedCrossRefGoogle Scholar
  8. Blaese RM, Andrson WF, Culver KW, Rosenberg SA (1990) The ADA human gene therapy clinical protocol. Hum Gene Ther 1: 327–362.CrossRefGoogle Scholar
  9. Blaese RM, Culver KW, Miller AD, Carter CS, Fleisher T, Clerici M, Shearer G, Chang L, Chiang Y, Tolstoshev P (1995) T lymphocyte-directed gene therapy for ADA-SCID: initial trial results after 4 years. Science 270: 475–480.PubMedCrossRefGoogle Scholar
  10. Bonini C, Ferrari G, Verzeletti S, Servida P, Zappone E, Ruggieri L, Ponzoni M, Rossini S, Mavilio F, Traversari C, Bordignon C (1997) HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science. 276(5319): 1719–1724.PubMedCrossRefGoogle Scholar
  11. Bordignon C, Bonini C, Verzeletti S, Nobili N, Maggioni D, Traversari C, Giavazzi R, Servida P, Zappone E, Benazzi E (1995a) Transfer of the HSV-tk gene into donor peripheral blood lymphocytes for in vivo modulation of donor anti-tumor immunity after allogeneic bone marrow transplantation. Hum Gene Ther 6: 813–819.PubMedCrossRefGoogle Scholar
  12. Bordignon C, Notarangelo LD, Nobili N, Ferrari G, Casorati G, Panina P, Mazzolari E, Maggioni D, Rossi C, Servida P (1995b) Gene therapy in peripheral blood lymphocytes and bone marrow for ADA-immunodeficient patients. Science 270: 470–475.PubMedCrossRefGoogle Scholar
  13. Boucher RC, Knowles MR, Johnson LG, Olsen JC, Pickles R, Wilson JM, Engelhardt J, Yang Y, Grossman M (1994) Gene therapy for cystic fibrosis using El-deleted adenovirus: a phase I trial in the nasal cavity. The University of North Carolina at Chapel Hill. Hum Gene Ther 5: 615–639.PubMedCrossRefGoogle Scholar
  14. Burt K, Chema D, Timmons T (1997) Tracing the dissemination of adenoviral vectors in patient body fluids. J Mol Med 75:5; B28(86).Google Scholar
  15. Calarota S, Bratt G, Nordlund S, Hinkula J, Leandersson AC, Sandstrom E, Wahren B (1998) Cellular cytotoxic response induced by DNA vaccination in HIV-1-infected patients. Lancet. 351(9112): 1320–1325.PubMedCrossRefGoogle Scholar
  16. Caplen NJ, Alton EW, Middleton PG, Dorin JR, Stevenson BJ, Gao X, Durham SR, Jeffery PK, Hodson ME, Coutelle C (1995) Liposome-mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis. Nat Med 1: 39–46.PubMedCrossRefGoogle Scholar
  17. Chang MW, Barr E, Min-Min-Lu, Barton K, Leiden JM (1995a) Adenovirus-mediated over-expression of the cyclin/cyclin-dependent kinase inhibitor, p21 inhibits smooth muscle cell prolife-ration and neointima formation in the rat carotid artery model of balloon angioplasty. J Clin Invest 96(5): 2260–2268.PubMedCrossRefGoogle Scholar
  18. Chang MW, Barr E, Seltzer J, Jiang YQ, Nabel GJ, Nabel EG, Parmacek MS, Leiden JM (1995b) Cytostatic gene therapy for vascular proliferative disorders with a constitutively active form of retinoblastoma gene product. Science 267(5197): 518–522.PubMedCrossRefGoogle Scholar
  19. Conry RM, LoBuglio AF, Curiel DT (1996) Polynucleotide-mediated immunization therapy of cancer. Semin Oncol 23: 135–147.PubMedGoogle Scholar
  20. Cornetta K, Srour EF, Moore A, Davidson A, Broun ER, Hromas R, Moen RC, Morgan RA, Rubin L, Anderson WF, Hoffman R, Tricot G (1996) Retroviral gene transfer in autologous bone marrow transplantation for adult acute leukemia. Hum Gene Ther 7(11); 1323–1329.PubMedCrossRefGoogle Scholar
  21. Crystal RG (1995) Transfer of genes to humans: early lessons and obstacles to success. Science 270: 404–410.PubMedCrossRefGoogle Scholar
  22. Crystal RG, McElvaney NG, Rosenfeld MA, Chu CS, Mastrangeli A, Hay JG, Brody SL, Jaffe HA, Eissa NT and Danel C (1994) Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis. Nat Genet 8: 42–51.PubMedCrossRefGoogle Scholar
  23. Crystal RG, Jaffe A, Brody S, Mastrangeli A, McElvaney NG, Rosenfeld M, Chu CS, Danel C, Hay J, Eissa T (1995) A phase 1 study, in cystic fibrosis patients, of the safety, toxicity, and biological efficacy of a single administration of a replication deficient, recombinant adenovirus carrying the cDNA of the normal cystic fibrosis transmembrane conductance regulator gene in the lung. Hum Gene Ther 6: 643–666.PubMedCrossRefGoogle Scholar
  24. Culver KW, Osborne WR, Miller AD, Fleisher TA, Berger M, Anderson WF, Blaese RM (1991) Correction of ADA deficiency in human T lymphocytes using retroviral-mediated gene transfer. Transplant Proc 23(1 Pt 1): 170–171PubMedGoogle Scholar
  25. Culver KW, Anderson WF, Blaese RM. (1991) Lymphocyte gene therapy. Hum Gene Ther 2(2): 107–109.PubMedCrossRefGoogle Scholar
  26. Culver KW, Blaese RM (1994) Gene therapy for cancer. Trends Genet 10: 174–178.PubMedCrossRefGoogle Scholar
  27. Davidson A, Morey S, Musk AW, et al. (1997) Gene therapy or therapy by intratumoral cytokines by infusion in mesothelioma patients. Lung Cancer 18 (suppl. 2):94CrossRefGoogle Scholar
  28. Deisseroth AB, Kavanagh J, Champlin R (1994) Clinical protocol: Use of safety-modified retro viruses to introduce chemotherapy resistance sequences into normal hematopoietic cells for chemoprotection during the therapy of ovarian cancer: a pilot trial. Hum Gene Ther 5: 1507–1522.PubMedCrossRefGoogle Scholar
  29. Deshane J, Siegal GP, Wang MH, Wright M, Bucy RP, Alvarez RD and Curiel DT (1997) Transduc-tional efficacy and safety of an intraperitoneally delivered adenovirus encoding an anti Erbb 2 intracellular single chain antibody for ovarian cancer gene therapy. Gynecologic Oncology 64(3): 378–385.PubMedCrossRefGoogle Scholar
  30. Dichek DA, Neville RF, Zwiebel JA, Freeman SM, Leon MB, Anderson WF (1989) Seeding of intravascular stents with genetically engineered endothelial cells. Circulation 80: 1347–1353.PubMedCrossRefGoogle Scholar
  31. Dunbar C, Kohn D, Karlsson S, Barton N, Brady R, Cottier-Fox M, Crooks G, Emmons R, Esplin J, Leitman S, Lenarsky C, Nolta J, Parkman R, Pensiero M, Schifmann R, Tolstoshev P, Weinberg K (1996) Retroviral mediated transfer of the cDNA for human glucocerebrosidase into hematopoietic stem cells of patients with Gaucher disease. A phase I study. Hum Gene Ther 7: 231–253.PubMedCrossRefGoogle Scholar
  32. During M (1996a) Gene therapy chronology. Science 273: 416–417.PubMedCrossRefGoogle Scholar
  33. During MJ (1996b) Gene trial in New Zealand. Lancet 348: 618PubMedCrossRefGoogle Scholar
  34. Engel BC, Laws HJ, Buttlies B, Kahn T, Gobel U, Burdach SEG (1998) Induction of a CD3+/CD56+ lymphocyte population following gene therapy with transgenic IL-2 secreting fibroblasts in a child with peripheral neuroectodermal malignancy. Med Pediatr Oncol 31(2): 56–60.PubMedCrossRefGoogle Scholar
  35. European Working Group of Gene Therapy E (1996) Newsletter No. 5.Google Scholar
  36. Evans CH, Mankin HJ, Ferguson AB Jr, Robbins PD, Ghivizzani SC, Herndon JH, Kang R, Bahnson AB, Barranger JA, Elders EM, Gay S, Tomaino MM, Wasko MC, Watkins SC, Whiteside TL, Glorioso JC, Lotze MT, Wright TM (1996) Clinical trial to assess the safety, feasibility, and efficacy of transferring a potentially anti-arthritic cytokine gene to human joints with rheumatoid arthritis. Hum Gene Ther 7: 1261–1306.PubMedCrossRefGoogle Scholar
  37. Feldman LJ, Isner JM (1995) Gene therapy for the vulnerable plaque. J Am Coll Cardiol 26: 826–835.PubMedCrossRefGoogle Scholar
  38. Fenton RT, Sznol M, Luster DG, Taub DD, Longo DL (1995) A phase I trial of B7-transfected or parental lethally irradiated allogeneic melanoma cell lines to induce cell-mediated immunity against tumor-associated antigen presented by HLA-A2 or HLA-A1 in patients with stage IV melanoma. NCI protocol T93-0161. BRMP protocol 9401. Hum Gene Ther 6: 87–106.PubMedCrossRefGoogle Scholar
  39. Flotte TR, Conrad C, Reynolds TZ (1995) Preclinical evaluation of AAV vectors expressing the human CFTR cDNA. J Cell Biochem suppl 21A:364C366–112. (Abstract)Google Scholar
  40. Flotte TR, Carter B, Conrad C, Guggino W, Reynolds T, Rosenstein B, Taylor G, Waiden S, Wtezel R (1996) A phase 1 study of an adeno-associated virus-CFTR gene vector in adult CF patients with mild lung disease. Hum Gen Ther 7(9): 1145–1159.CrossRefGoogle Scholar
  41. Freeman SM, McCune MC, Robinson E (1992) Treatment of ovarian cancer using HSV-TK gene-modified vaccine. Hum Gene Ther 3:342.Google Scholar
  42. Gahery-Segard H, Molinier-Frenkel V, Le Boulaire C, Saulnier P, Opolon P, Lengagne R, Gautier E, Le Cesne A, Zitvogel L, Venet A, Schatz C, Courtney M, Le Chevalier T, Tursz T, Guillet JG, Farace F (1997) Phase I trial of recombinant adenovirus gene transfer in lung cancer. Longitudinal study of the immune responses to transgene and viral products. J Clin Invest 100(9): 2218–2226.PubMedCrossRefGoogle Scholar
  43. Galpin JE, Casciato DA, Richards SB (1994) A phase I clinical trial to evaluate the safety and biological activity of HIV-IT (TAF) (HIV-HIIBenv-transduced, autologous fibroblasts) in asymptomatic HIV-1 infected subjects. Hum Gene Ther 5(8): 997–1017.PubMedCrossRefGoogle Scholar
  44. Gänsbacher B, Rosenthal FM, Zier K (1993) Retroviral vector-mediated cytokine-gene transfer into tumor cells. Cancer Invest 11: 345–354.PubMedCrossRefGoogle Scholar
  45. Gill DR, Southern KW, Mofford KA, Seddon T, Huang L, Sorgi F, Thomson A, Macvinish LJ, Ratcliff R, Bilton D, Lane DJ, Littlewood JM, Webb AK, Middleton PG, Colledge WH, Cuthbert AW, Evans MJ, Higgins CF, Hyde SC (1997) A placebo controlled study of liposome mediated gene transfer to the nasal epithelium of patients with cystic fibrosis. Gene Therapy 4(3): 199–209.PubMedCrossRefGoogle Scholar
  46. Ginsberg HS Hrsg. (1984) The adenoviruses. New York: Plenum Press.Google Scholar
  47. Grossman M, Raper SE, Kozarsky K, Stein EA, Engelhardt JF, Muller D, Lupien PJ, Wilson JM (1994) Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolaemia. Nat Genet 6: 335–341.PubMedCrossRefGoogle Scholar
  48. Grossman M, Rader DJ, Muller DW, Kolansky DM, Kozarsky K, Clark BJ 3rd, Stein EA, Lupien PJ, Brewer HB Jr, Raper SE, Wilson JM (1995) A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolaemia. Nat Med 1(11): 1148–1154.PubMedCrossRefGoogle Scholar
  49. Habib NA, Ding SF, el-Masry R, Mitry RR, Honda K, Michail NE, Dalla-Serra G, Izzi G, Greco L, Bassyouni M, el-Toukhy M, Abdel-Gaffar Y (1996) Preliminary report: the short-term effects of direct p53 DNA injection in primary hepatocellular carcinomas. Cancer Detect Prev 20(2): 103–107.PubMedGoogle Scholar
  50. Hallek M, Girod A, Braun-Falco M, Wendtner C-M, Bogedain C, Hörer M (1998) Recombinant adeno-associated virus vectors. Curr Res Mol Ther 1: 417–430Google Scholar
  51. Harris JD, Lemoine NR (1996) Strategies For Targeted Gene Therapy. Trends in Genetics 12(10): 400–405.PubMedCrossRefGoogle Scholar
  52. Hatzoglou M, Lamers W, Bosch F, Wynshaw BA, Clapp DW, Hanson RW (1990) Hepatic gene transfer in animals using retroviruses containing the promoter from the gene for phosphoenolpyruvate carboxykinase. J Biol Chem 265: 17285–17293.PubMedGoogle Scholar
  53. Haubrich R, McCutchan JA, Holdredge R, Heiner L, Merritt J, Merchant B (1995) An open label, phase I/II clinical trial to evaluate the safety and biological activity of HIV-IT (V) (HIV-1(IIIB)(env/rev) retroviral vector) in HIV-1-infected subjects. Hum Gene Ther 6(7): 941–955.PubMedCrossRefGoogle Scholar
  54. Hay JG, McElvaney NG, Herena J, Crystal RG (1995) Modification of nasal epithelial potential differences of individuals with cystic fibrosis consequent to local administration of a normal CFTR cDNA adenovirus gene transfer vector. Hum Gene Ther 6: 1487–1496.PubMedCrossRefGoogle Scholar
  55. Hesdorffer C, Antman K, Bank A, Fetell M, Mears G, Begg M (1994) Clinical protocol: Human MDR gene transfer in patients with advanced cancer. Hum Gene Ther 5: 1151–1160.PubMedCrossRefGoogle Scholar
  56. Hesdorffer C, Ayello J, Ward M, Kaubisch A, Vahdat L, Balmaceda C, Garrett T, Fetell M, Reiss R, Bank A, Antman K (1998) Phase I trial of retroviral-mediated transfer of the human MDR1 gene as marrow chemoprotection in patients undergoing high-dose chemotherapy and autologous stem-cell transplantation. J Clin Oncol. 16(1): 165–172.PubMedGoogle Scholar
  57. Hijiya N, Zhang J, Ratajczak MZ, Kant JA, DeRiel K, Herlyn M, Zon G, Gewirtz AM (1994) Biologic and therapeutic significance of MYB expression in human melanoma. Proc Natl Acad Sci U S A 91: 4499–4503.PubMedCrossRefGoogle Scholar
  58. Hoogerbrugge PM, Van Beusechem VW, Kaptein LC, Einerhand MP, Valerio D (1995) Gene therapy for adenosine deaminase deficiency. Br Med Bull 51:72–81.PubMedGoogle Scholar
  59. Hoogerbrugge PM, Van Beusechem VW, Fischer A, Debree M, le Deist F, Perignon JL, Morgan G, Gaspar B, Fairbanks LD, Skeoch CH, Moseley A, Harvey M, Levinsky RJ, Valerio D (1996) Bone marrow gene transfer in three patients with adenosine deaminase deficiency. Gene Ther 3: 179–183.PubMedGoogle Scholar
  60. Horowitz MS (1990) Adenoviridaee and their replication. In: Fields BN, Knipe DM, Herausg. Virology. New York Raven Press, 1679–1740.Google Scholar
  61. Huebner RJ, Rowe WP, Ward TG, et al. (1954) Adenoidal-pharyngeal-conjunctival agents. N Engl J Med 251:1077–1086.PubMedCrossRefGoogle Scholar
  62. Huehns TY, Krausz E, Mrochen S, Schmid M, Engelmann MG, Esin S, Schrittenloher P-K, Höfling B, Günzburg WH, Nikol S (in press) Neointimal growth can be influenced by local adventitial gene manipulation via a needle injection catheter. Atherosclerosis.Google Scholar
  63. Hui KM, Ang PT, Huang L, Tay SK (1997) Phase I study of immunotherapy of cutaneous métastases of human carcinoma using allogeneic and xenogeneic MHC DNA-liposome complexes. Gene Ther 4(8): 783–790.PubMedCrossRefGoogle Scholar
  64. Isner JM (1998) Arterial gene transfer of naked DNA for therapeutic angiogenesis: Early clinical results. Adv Drug Deliv Rev 30(1-3): 185–197.PubMedCrossRefGoogle Scholar
  65. Isner JM, Walsh K, Symes J, Pieczek A, Takeshita S, Lowry J, Rossow S, Rosenfield K, Weir L, Brogi E, Schainfeld R (1995) Arterial gene therapy for therapeutic angiogenesis in patients with peripheral artery disease. Circulation 91: 2687–2692.PubMedCrossRefGoogle Scholar
  66. Isner JM, Pieczek A, Schainfeld R, Blair R, Haley L, Asahara T, Rosenfield K, Razvi S, Walsh K, Symes JF (1996a) Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb. Lancet 348: 370–374.PubMedCrossRefGoogle Scholar
  67. Isner JM, Walsh K, Symes J, Pieczek A, Takeshita S, Lowry J, Rosenfield K, Weir L, Brogi E, Juragyj D (1996b) Clinical Protocol: Arterial gene transfer for therapeutic angiogenesis in patients with perpheral artery disease. Hum Gene Ther 7: 959–988.PubMedCrossRefGoogle Scholar
  68. Isner JM, Walsh K, Rosenfield K, Schainfeld R, Asahara T, Hogan K, Pieczek A (1996c) Arterial gene therapy for restenosis. Hum Gene Ther 7: 989–1011.PubMedCrossRefGoogle Scholar
  69. Izquierdo M, Cortes ML, Martin V, de Felipe P, Izquierdo JM, Perez-Higueras A, Paz JF, Isla A, Blazquez MG (1997) Gene therapy in brain tumours: implications of the size of glioblastoma on its curability. Acta Neurochir Suppl Wien 68: 111–117.Google Scholar
  70. Jantscheff P, Bongartz G, Dietrich PY, Schatz C, Mehtali M, Courtney M, Herrmann R, Rochlitz C (1997) Phase I study of cytokine-transfected xenogeneic cells (Vero-IL2) in patients with metastatic solid tumors. J Mol Med 75: B31(98)Google Scholar
  71. Kircheis R, Kichler A, Wallner G, Kursa M, Ogris M, Felzmann T, Buchberger M, Wagner E (1997) Coupling of cell binding ligands to polyethylenimine for targeted gene delivery. Gene Ther 4(5): 409–418.PubMedCrossRefGoogle Scholar
  72. Knowles MR, Hohneker KW, Zhou Z, Olsen JC, Noah TL, Hu PC, Leigh MW, Engelhardt JF, Edwards LJ, Jones KR (1995) A controlled study of adenoviral-vector-mediated gene transfer in the nasal epithelium of patients with cystic fibrosis. N Engl J Med 333: 823–831.PubMedCrossRefGoogle Scholar
  73. Kohn D, Weinberg KI, Parkman P, Lenarsky C, Crooks GM, Shaw K, Hanley ME, Lawrence K, Annett G, Brooks JS, Wara D, Elder M, Bowen T, Hershfield MS, Berenson RI, Moen RC, Mullen CA, Blaese RM (1993) Gene therapy for naonates with ADA-deficient SCID by retroviral-me-diated transfer of the human ADA cDNA into umbilical cord CD34+ cells. Blood 82 (suppl. 1): 315a.Google Scholar
  74. Kohn DB, Weinberg KI, Nolta JA, Heiss LN, Lenarsky C, Crooks GM, Hanley ME, Annett G, Brooks JS, el KA (1995) Engraftment of gene-modified umbilical cord blood cells in neonates with adenosine deaminase deficiency. Nat Med 1: 1017–1023.PubMedCrossRefGoogle Scholar
  75. Kohn DB, Hershfield `MS, Corbonaro D, Shigeoka A, Brooks J, Smogorzewska EM, Barsky LW, Chan R, Burotto F, Annett G, Nolta JA, Crooks G, Kapoor N, Elder M, Wara D, Bowen T, Madsen E, Snyder FF, Bastian J, Muul L, Blaese RM, Weinberg K, Parkman R (1998) T lymphocytes with a normal ADA gene accumulate after transplantation of transduced autologous umbilical cord blood CD34+ cells in ADA-deficient SCID neonates. Nat Med 4(7): 775–780.PubMedCrossRefGoogle Scholar
  76. Kutryk MJB, de Groot MR, van den Brand M, Hamburger JN, van der Giessen WJ, Foley DP, de Feyter PJ, von Birgelen C, Camenzind E, Serruys PW (1997) Feasibility of the local delivery of antisense oligonucleotide against c-myc for the prevention of in-stent restenosis: acute results of the Thoraxcentre „ITALICS“ trial. 14th Congress of the European Society of Cardiology, Stockholm p2918.Google Scholar
  77. Link CJ, Moorman D, Seregina T, Levy JP, Schabold KJ (1995) A phase I trial of in vivo gene therapy with the Herpes simplex thymidine kinase ganciclovir system for the treatment of refractory or recurrent ovarian cancer. Cancer Gene Therapy 2: 230–231.Google Scholar
  78. Liu JM, Young NS, Walsh CE, Cottier-Fox CE, Carter C, Dunbar C, Barrett AJ, Emmons R (1997) Retroviral mediated gene transfer of the Fanconi anemia complementation group C gene to hematopietic progenitors of goup C patients. Hum Gene Ther 8(14): 1715–1730.PubMedCrossRefGoogle Scholar
  79. Liu JM (1998) Gene transfer for the eventuel treatment of Fanconi’s anemia. Semin Hematol 35(2): 168–179.PubMedGoogle Scholar
  80. Lotze MT, Rubin JT (1995) Report of the Recombinant DNA Advisory Committee (RAC) of the National Institutes of Health (NIH). 9209–033.Google Scholar
  81. Lotze MT, Rubin JT, Carty S, Edington H, Ferson P, Landreneau R, Pippin B, Posner M, Rosenfelder D, Watson C (1994) Gene therapy of cancer: a pilot study of IL-4-gene-modified fibroblasts admixed with autologous tumor to elicit an immune response. Hum Gene Ther 5: 41–55.PubMedCrossRefGoogle Scholar
  82. Lu DR, Zhou JM, Zheng B, Qiu XF, Xue JL, Wang JM, Meng PL, Han FL, Ming BH, Wang XP (1993) Stage I clinical trial of gene therapy for hemophilia B. Sei China B 36(11): 1342–1351.Google Scholar
  83. MacGregor RR, Boyer JD, Ugen KE, Lacy KE, Gluckman SJ, Bagarazzi ML, Chattergoon MA, Baine Y, Higgins TJ, Ciccarelli RB, Coney LR, Ginsberg RS, Weiner DB (1998) First human trial of a DNA-based vaccine for treatment of human immunodeficiency virus type 1 infection: safety and host response. J Infect Dis 178(1): 92–100.PubMedCrossRefGoogle Scholar
  84. Mackensen A, Veelken H, Lahn M, Wittnebel S, Becker D, Kohler G, Kulmburg P, Brennscheidt U, Rosenthal F, Franke B, Mertelsmann R, Lindemann A (1997) Induction of tumor-specific cytotoxic T lymphocytes by immunization with autologous tumor cells and interleukin-2 gene transfected fibroblasts. J Mol Med 75(4): 290–296.PubMedCrossRefGoogle Scholar
  85. Malech HL, Maples PB, Whiting-Theobald N, Linton GF, Sekhsaria S, Vowells SJ, Li F, Miller JA, DeCarlo E, Holland SM, Leitman SF, Carter CS, Butz RE, Read EJ, Fleisher TA, Schneiderman RD, Van Epps DE, Spratt SK, Maack CA, Rokovich JA, Cohen LK, Gallin-JI (1997) Prolonged production of NADPH oxidase-corrected granulocytes after gene therapy of chronic granulo-matous disease. Proc Natl Acad Sci USA 94(22): 12133–12138.PubMedCrossRefGoogle Scholar
  86. Marshall E (1996) New Zealand’s leap into gene therapy. Science 271: 1489–1490.PubMedCrossRefGoogle Scholar
  87. McElvaney NG, Crystal RG (1995) IL-6 release and airway administration of human CFTR cDNA adenovirus vector [2]. Nat Med 1: 182–184.PubMedCrossRefGoogle Scholar
  88. Merrouche Y, Negrier S, Bain C, Combaret V, Mercatello A, Coronel B, Moskovtchenko JF, Tolstoshev P, Moen R, Philip T (1995) Clinical application of retroviral gene transfer in oncology: results of a French study with tumor-infiltrating lymphocytes transduced with the gene of resistance to neomycin. J Clin Oncol 13: 410–418.PubMedGoogle Scholar
  89. Mukherjee S, Haenel T, Epton M (1997) Intralesional vaccinia virus-interleukin-2 (VV-IL-2) gene therapy in malignant mesothelioma (MM). Lung Cancer 18(suppl. 1): 236.CrossRefGoogle Scholar
  90. Nabel EG, Gordon D, Yang ZY, Xu L, San H, Plautz GE, Wu BY, Gao X, Huang L, Nabel GJ (1992) Gene transfer in vivo with DNA-liposome complexes: lack of autoimmunity and gonadal localization. Hum Gene Ther 3: 649–656.PubMedCrossRefGoogle Scholar
  91. Nabel EG, Yang Z, Müller D, Chang AE, Gao X, Huang L, Cho KJ, Nabel GJ (1994) Safety and toxicity of catheter gene delivery to the pulmonary vasculature in a patient with metastatic melanoma. Hum Gene Ther 5: 1089–1094.PubMedCrossRefGoogle Scholar
  92. Nabel GJ, Chang A, Nabel EG, Plautz G, Fox BA, Huang L, Shu S. (1992) Immunotherapy of malignancy by in vivo gene transfer into tumors. Human Gene Therapy 3: 399–410.CrossRefGoogle Scholar
  93. Nabel GJ, Nabel EG, Yang ZY, Fox BA, Plautz GE, Gao X, Huang L, Shu S, Gordon D, Chang AE (1993) Direct gene transfer with DNA-liposome complexes in melanoma: expression, biologic activity, and lack of toxicity in humans. Proc Natl Acad Sci USA 90: 11307–11311.PubMedCrossRefGoogle Scholar
  94. Nabel GJ, Chang AE, Nabel EG, Plautz GE, Ensminger W, Fox BA, Feigner P, Shu S, Cho K (1994) Immunotherapy for cancer by direct gene transfer into tumors. Hum Gene Ther 5: 57–77.PubMedCrossRefGoogle Scholar
  95. Nabel GJ, Yang ZY, Nabel EG, Bishop K, Marquet M, Feigner PL, Gordon D, Chang AE (1995) Direct gene transfer for treatment of human cancer. Ann N Y Acad Sci 772: 227–231.PubMedCrossRefGoogle Scholar
  96. Nikol S, Huehns TY, Krausz E, Armeanu S, Engelmann MG, Winder D, Salmons B, Höfling B (in press) Needle injection catheter delivery of the gene for an antibacterial agent inhibits neointimal formation. Gene TherGoogle Scholar
  97. O’Shaughnessy JA, Cowan KH, Nienhuis AW, McDonagh KT, Dorrentino Bp, Bunbar CE, Chiang Y, Wilson W, Goldspiel B, Köhler D, Cottier-Fox M, Leitman S, Gottesman M, Pastan I, Denicoff A, Noone M, Gress R (1994) Clinical protocol: Retroviral mediated transfer of the human multidrug resistance gene (MDR-1) into hematopoietic stem cells during autologous transplantation after intensive chemotherapy for metastatic breast cancer. Hum Gen Ther 5: 891–911.CrossRefGoogle Scholar
  98. Oldfield EH, Ram Z, Chiang Y, Blaese RM (1995) Intrathecal gene therapy for the treatment of leptomeningeal carcinomatosis. GTI0108. A phase I/II study. Hum Gene Ther 6(1): 55–85.PubMedCrossRefGoogle Scholar
  99. Onodera M, Ariga T, Kawamura N, Kobayashi I, Ohtsu M, Yamada M, Tame A, Furuta H, Okano M, Matsumoto S, Kotani H, McGarrity GJ, Blaese RM, Sakiyama Y (1998) Successful peripheral T-lymphocyte-directed gene transfer for a patient with severe combined immune deficiency caused by adenosine deaminase deficiency. Blood 91: 30–36PubMedGoogle Scholar
  100. Parmiani G, Arienti F, Sulesuso J, Melani C, Colombo MP, Ramakrishna V, Belli F, Mascheroni L, Rivoltini L and Cascinelli N (1996) Cytokine based gene therapy of human tumors: an overview. Folia Biologica 42(6): 305–309.PubMedGoogle Scholar
  101. Porteous DJ, Dorin JR, McLachlan G, Davidson Smith H, Davidson H, Stevenson BJ, Carothers AD, Wallace WA, Moralee S, Hoenes C, Kallmeyer G, Michaelis U, Naujoks K, Ho LP, Samways JM, Imrie M, Greening AP, Innes JA (1997) Evidence for safety and efficacy of DOTAP cationic liposome mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis. Gene Ther 4(3): 210–218.PubMedCrossRefGoogle Scholar
  102. Qiu X, Lu D, Zhou J, Wang J, Yang J, Meng P, Hsueh JL (1996) Implantation of autologous skin fibroblast genetically modified to secrete clotting factor IX partially corrects the hemorrhagic tendencies in two hemophilia B patients. Chin Med J Engl 109(11): 832–839.PubMedGoogle Scholar
  103. Ram Z, Culver K, Oshiro E (1995) Summary of results and conclusions of the gene therapy of malignant brain tumors: Clinical study. Journal of Neurosurgery 82: 343A.Google Scholar
  104. Recombinant DNA Advisory Committee (RAC) der NIH. (1995) Data management scientific report and status report, Stand 2.6.1995.Google Scholar
  105. Riddell SR, Elliott M, Lewinsohn DA, Gilbert MJ, Wilson L, Manley SA, Lupton SD, Overell RW, Reynolds TC, Corey L, Greenberg PD (1996) T-cell mediated rejection of gene-modified HIV-specific cytotoxic T lymphocytes in HIV-infected patients. Nat Med 2(2): 216–223.PubMedCrossRefGoogle Scholar
  106. Rosenberg SA (1992) Karnofsky Memorial Lecture. The immunotherapy and gene therapy of cancer. J Clin Oncol 10: 180–199.PubMedGoogle Scholar
  107. Rosenberg SA, Aebersold P, Cornetta K, Kasid A, Morgan RA, Moen R, Karson EM, Lotze MT, Yang JC, Topalian SL (1990) Gene transfer into humans-immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction. N Engl J Med 323: 570–578.PubMedCrossRefGoogle Scholar
  108. Rosenberg SA, Yannelli JR, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, Parkinson DR, Seipp CA, Einhorn JH, White DE (1994) Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2. J Natl Cancer Inst 86: 1159–1166.PubMedCrossRefGoogle Scholar
  109. Roth JA (1996a) Modification of tumor suppressor gene expression in non small cell lung cancer (Nsclc) with a retroviral vector expressing wildtype (normal) p53. Human Gene Therapy 7(7): 861–874.PubMedCrossRefGoogle Scholar
  110. Roth JA, Nguyen D, Lawrence DD, Kemp BL, Carrasco CH, Ferson DZ, Hong WK, Komaki R, Lee JJ, Nesbitt JC, Pisters KMW, Putnam JB, Schea R, Shin DM, Walsh GL, Dolormente MM, Han CI, Martin FD, Yen N, Xu K, Stephens LC, McDonnell TJ, Mukhopadhyay T, Cai D (1996b) Retrovirus mediated wild type p53 gene transfer to tumors of patients with lung cancer. Nat Med 2(9): 985–991.PubMedCrossRefGoogle Scholar
  111. Roth JA, Cristiano RJ (1997a) Gene therapy for cancer: What have we done and where are we going. Journal of the National Cancer Institute 89(1): 21–39.PubMedCrossRefGoogle Scholar
  112. Roth JA (1997b) 33rd American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract).Google Scholar
  113. Rubin J, Charboneau JW, Reading C, Kovach JS (1994) Phase I study of immunotherapy of hepatic metastases of colorectal carcinoma by direct gene transfer. Hum Gene Ther 5(11): 1385–1399.PubMedCrossRefGoogle Scholar
  114. Sakiyama Y (1996a) Clinical study of gene therapy for ADA deficiency. Aerugi 45:621–626.Google Scholar
  115. Sakiyama Y (1996b) Gene therapy for adenosine deaminase deficiency. Hokkaido Igaku Zasshi 71:27–32.PubMedGoogle Scholar
  116. Salmons B, Gunzburg WH (1993) Targeting of retroviral vectors for gene therapy. Hum Gene Ther 4(2): 129–41.PubMedCrossRefGoogle Scholar
  117. Schadendorf D, Czarnetzki BM, Wittig B (1995) Interleukin-7, interleukin-12, and GM-CSF gene transfer in patients with metastatic melanoma. J Mol Med 73: 473–477.PubMedCrossRefGoogle Scholar
  118. Simons M, Edelman ER, DeKeyser JL, Langer R, Rosenberg RD (1992) Antisense c-myb oligonucleotides inhibit intimai arterial smooth muscle cell accumulation in vivo. Nature 359: 67–70.PubMedCrossRefGoogle Scholar
  119. Sobol RE, Fakhrai H, Shawler D, Gjerset R, Dorigo O, Carson C, Khaleghi T, Koziol J, Shiftan TA, Royston I (1995) Interleukin-2 gene therapy in a patient with glioblastoma. Gene Ther 2: 164–167.PubMedGoogle Scholar
  120. Son K, Huang L (1994) Exposure of human ovarian carcinoma to cisplatin transiently sensitizes the tumor cells for liposome-mediated gene transfer. Proc Natl Acad Sci USA 91: 12669–12672.PubMedCrossRefGoogle Scholar
  121. Sterman DH, Treat J, Litzky LA, Amin KM, Coonrod L, Molnar-Kimber K, Recio A, Knox L, Wilson JM, Albelda SM, Kaiser LR (1998a) Adenovirus-mediated herpes simplex virus thymidine kinase/ganciclovir gene therapy in patients with localized malignancy: results of a phase I clinical trial in malignant mesothelioma. Hum Gene Ther 9(7): 1083–1092.PubMedCrossRefGoogle Scholar
  122. Sterman DH, Kaiser LR, Albelda SM (1998b) Gene therapy for malignant pleural mesothelioma. Gene Ther 12: 553–568.Google Scholar
  123. Stopeck AT, Hersh EM, Akporiaye ET, Harris DT, Grogan T, Unger E, Warneke J, Schlüter SF, Stahl S (1997) Phase I study of direct gene transfer of an allogeneic histocompatibility antigen, HLA-B7, in patients with metastatic melanoma. J Clin Oncol 15: 341–349.PubMedGoogle Scholar
  124. Sun Y, Jurgovsky K, Moller P, Alijagic S, Dorbic T, Georgieva J, Wittig B, Schadendorf D (1998) Vaccination with IL-12 gene-modified autologous melanoma cells: preclinical results and a first clinical phase I study. Gene Ther 5(4): 481–90.PubMedCrossRefGoogle Scholar
  125. Tait DL, Obermiller PS, Redlin-Frazier S, Jensen RA, Welsch P, Dann J, King M.C, Johnson DH, Holt J (1997) A phase I trial of retroviral BRCAlsv gene therapy in ovarian cancer. Clinical Cancer Research 3: 1959–1968PubMedGoogle Scholar
  126. Tan Y, Xu M, Wang W, Zhang F, Li D, Xu X, Gu J, Hoffman RM (1996) IL-2 gene therapy of advanced lung cancer patients. Anticancer Res 16: 1993–1998.PubMedGoogle Scholar
  127. Tsang KY, Zaremba S, Nieroda CA, Zhu MZ, Hamilton JM, Schlom J (1995) Generation of human cytotoxic T-cell specific for human carcinoembryonic antigen (CEA) epitopes from patients immunized with recombinant vaccinia-CEA (rV-CEA) vaccine. J Natl Cancer Inst 87: 982–990.PubMedCrossRefGoogle Scholar
  128. Tursz T, Cesne AL, Baldeyrou P, Gautier E, Opolon P, Schatz C, Pavirani A, Courtney M, Lamy D, Ragot T, Saulnier P, Andremont A, Monier R, Perricaudet M, Le Chevalier T (1996) Phase I study of a recombinant adenovirus-mediated gene transfer in lung cancer patients. J Natl Cancer Inst 88: 1857–1863.PubMedCrossRefGoogle Scholar
  129. Veelken H, Mackensen A, Lahn M, Kohler G, Becker D, Franke B, Brennscheidt U, Kulmburg P, Rosenthal FM, Keller H, Hasse J, Schultze Seemann W, Farthmann EH, Mertelsmann R, Lindemann A (1997) A phase-I clinical study of autologous tumor cells plus interleukin-2-gene-transfected allogeneic fibroblasts as a vaccine in patients with cancer. Int J Cancer 70: 269–277.PubMedCrossRefGoogle Scholar
  130. Waddill W, Wright W, linger E, Stopeck A, Akporiaye E, Harris D, Grogan T, Schluter S, Hersh E, Stahl S (1997) Human gene therapy for melanoma: Ct guided interstitial injection. American Journal of Roentgenology 169(1): 63–67.PubMedCrossRefGoogle Scholar
  131. Wagner E, Zenke M, Cotten M, Beug H, Birnstiel ML (1990) Transferrin-polycation conjugates as carriers for DNA uptake into cells. Proc Natl Acad Sci USA 87(9): 3410–3414.PubMedCrossRefGoogle Scholar
  132. Walker R, Bechtel CM, Natarajan V, Baseler M, Metcalf JA, Stevens R, Blaese RM, Davey RT, Falloon J, Polis MA (1995) Adoptive transfer of genetically modified, HIV-specific, syngeneic cytotoxic T lymphocytes (CTL) in HIV discordant identical twins. 3rd Conference on Retroviruses and Opportunistic Infections. Washington, DC: Abstract 404.Google Scholar
  133. Weber F, Bojar H, Priesack HB, Floeth F, Lenartz D, Kiwit J, Bock W (1997) Gene therapy of glioblastoma — one year clinical experience with ten patients. JMM 75: B40. (Abstract).Google Scholar
  134. Welsh MJ, Zabner J, Graham SM, Smith AE, Moscicki R, Wadsworth S (1995) Adenovirus-mediated gene transfer for cystic fibrosis: Part A. Safety of dose and repeat administration in the nasal epithelium. Part B. Clinical efficacy in the maxillary sinus. Hum Gene Ther 6: 205–218.PubMedCrossRefGoogle Scholar
  135. Wiley Stand 1.12.1998, Wiedergabe mit Erlaubnis von Wiley J. Gene Medicine. Website: http://www.wiley.co.uk/genmed.Google Scholar
  136. Wilson JM (1995) Report of the Recombinant DNA Advisory Committee (RAC) of the National Institutes of Health (NIH).Google Scholar
  137. Woffendin C, Ranga U, Yang Z, Xu L, Nabel GJ (1996) Expression of a protective gene-prolongs survival of T cells in human immunodeficiency virus-infected patients. Proc Natl Acad Sci USA 93: 2889–2894.PubMedCrossRefGoogle Scholar
  138. Zabner J, Couture LA, Gregory RJ, Graham SM, Smith AE, Welsh MJ (1993) Adenovirus-mediated gene transfer transiently corrects the chloride transport defect in nasal epithelia of patients with cystic fibrosis. Cell 75: 207–216.PubMedCrossRefGoogle Scholar
  139. Zabner J, Ramsey BW, Meeker DP, Aitken ML, Balfour RP, Gibson RL, Launspach J, Moscicki RA, Richards SM, Standaert TA (1996) Repeat administration of an adenovirus vector encoding cystic fibrosis transmembrane conductance regulator to the nasal epithelium of patients with cystic fibrosis. J Clin Invest 97: 1504–1511.PubMedCrossRefGoogle Scholar
  140. Ziegner UH, Peters G, Jolly DJ, Mento SJ, Galpin J, Prussak CE, Barber JR, Hartnett DE, Bohart C, Klump W (1995) Cytotoxic T-lymphocyte induction in asymptomatic HIV-1-infected patients immunized with Retrovector-transduced autologous fibroblasts expressing HIV-HUB Env/Rev proteins. AIDS. 9(1): 43–50.PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2001

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  • S. Nikol
  • M. Hallek

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