Aktuelle Urol 2000; 31(7): 403-412
DOI: 10.1055/s-2000-9484
ÜBERSICHT
Georg Thieme Verlag Stuttgart · New York

Molekulare Aspekte des Harnblasenkarzinoms III: Gentherapie des Harnblasenkarzinoms

Gene Therapy of Bladder CancerP. Ardelt1, 2 , A. Böhle2
  • 1Genitourinary Oncology, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030
  • 2Laborgruppe Immuntherapie, Forschungszentrum Borstel u. Klinik für Urologie, Med. Universität Lübeck
Further Information

Publication History

Publication Date:
31 December 2000 (online)

Zusammenfassung

Gentherapie von Tumorerkrankungen ist die logische Folge der intensiven Bemühungen um die Aufklärung der genetischen Grundstruktur des Lebens und zu Krankheiten führender genetischer Defekte. Gentherapeutische Verfahren erlauben erstmals eine kausale Therapie des zu einer Erkrankung führenden Gendefekts. Die Gentherapie ist definitionsgemäß die Behandlung einer erworbenen oder angeborenen Krankheit durch Transfer von genetischem Material. - Dieser Artikel fasst die Grundlagen und Fortschritte in der Behandlung von Blasenkarzinomen durch Gentherapie zusammen und stellt sie systematisch dar. Verschiedene therapeutische Ansätze wurden entwickelt, wie z. B. der Transfer von Tumorsuppressorgenen zur Wiederherstellung der Zellzykluskontrolle in Tumorzellen, Suizid-Gentherapie zur selektiven Abtötung von Tumorzellen, Modulation des Immunsystems zur Induktion oder Verstärkung einer Immunantwort gegen den Tumor. Obwohl klinisch derzeit kein Verfahren etabliert ist, müssen die Fortschritte in der Gentherapie des Harnblasenkarzinoms aufgrund des hohen therapeutischen Potenzials aufmerksam verfolgt werden.

Abstract

Cancer gene therapy is an important consequence of the intense studies on the genetic base of life and genetic defects leading to diseases. Gene therapy firstly offered the ability to treat the actual gene defect leading to a disease. In the common definition gene therapy is the treatment of an acquired or inherited disease by transfer of genetic material. - This article reviews the basis and progresses in treating bladder cancer by gene therapy. Various therapeutic approaches have been developed for this, such as transfer of tumor suppressor genes to restore cell cycle control in tumor cells, suicide gene therapy to selectively eliminate tumor cells, modulation of immune response to enhance or initiate an immune response against a bladder tumor to name only a few. Although clinically none of these have been established the progresses should be thoroughly traced.

Literatur

  • 1 Avery O T, McLeod C M, McCarty M. Studies on the chemical nature of the substance inducing transformation of pneumococcal types. Induction of transformation by a deoxyribonucleic acid fraction isolated from Pneumococcus type III.  J Exp Med. 1944;  79 137-158
  • 2 Kmiec E B. Genomic targeting and genetic conversion in cancer therapy.  Semin Oncol. 1996;  23 (1) 188-193
  • 3 Kren B T, Cole-Strauss A, Kmiec E B, Steer C J. Target nucleotide exchange in the alkaline phosphatase gene of HuH-7 cells mediated by a chimeric RNA/DNA oligonucleotide.  Hepatology. 1997;  25 (6) 1462-1468
  • 4 Yanez R J, Porter A C. Gene targeting is enhanced in human cells overexpressing hRAD51.  Gene Therapy. 1999;  6 (7) 1282-1290
  • 5 Juliano R L, Akhtar S. Liposomes as drug delivery system for antisense oligonucleotides.  Antisense Res Dev. 1992;  2 165-176
  • 6 Chavany C D, Le D T, Couvreur P, Puisieux F, Helene C. Polyalkylcyanoacrylate nanoparticles as polymeric carriers for antisense oligonucleotides.  Pharm Res. 1992;  9 441-449
  • 7 Belair C D, Yeager T R, Lopez P M, Reznikoff C A. Telomerase activity: a biomarker of cell proliferation, not malignant transformation.  Proc Natl Acad Sci. 1997;  94 (25) 13677-13682
  • 8 Lim B, Apperley J F, Orkin S H, Williams D A. Long-term expression of human adenosine deaminase in mice transplanted with retrovirus-infected hematopoietic stem cells.  Proc Nat Acad Sci. 1989;  86 (22) 8892-8896
  • 9 Wang J, Ma Y, Knechte S J. Adenovirus-mediated gene transfer into rat cardiac allografts. Comparison of direct injection and perfusion.  Transplant. 1996;  61 (12) 1726-1729
  • 10 Li Y, Pong R C, Bergelson J M, Hall M C, Sagalowsky A I, Tseng C P, Wang Z, Hsieh J T. Loss of adenoviral receptor expression in human bladder cancer cells: a potential impact on the efficacy of gene therapy.  Cancer Res. 1999;  59 (2) 325-330
  • 11 Pan C X, Koeneman K S. A novel tumor-specific gene therapy for bladder cancer.  Med Hypotheses. 1999;  53 (2) 130-135
  • 12 Brandau S, Böhle A. Molekulare und genetische Mechanismen bei der Entstehung des Harnblasenkarzinoms.  Akt Urol. 2000;  31 149-156
  • 13 Morris Jr B D, Drazan K E, Csete M E, Werthman P E, Van Bree M P, Rosenthal J T, Shaked A. Adenoviral-mediated gene transfer to bladder in vivo.  J Urol. 1994;  152 (2 Pt 1) 506-509
  • 14 Lee S S, Eisenlohr L C, McCue P A, Mastrangelo M J, Lattime E C. Intravesical gene therapy: in vivo gene transfer using recombinant vaccina virus vectors.  Cancer Res. 1994;  54 (13) 3325-3328
  • 15 Bass C, Cabrera G, Elgavish A, Robert B, Siegal G P, Anderson S C, Maneval D C, Curiel D T. Recombinant adenovirus-mediated gene transfer to genitourinary epithelium in vitro and in vivo.  Cancer Gene Ther. 1995;  2 (2) 97-104
  • 16 Harimoto K, Sugimura K, Lee C R, Kuratsukuri K, Kishimoto T. In vivo gene transfer methods in the bladder without viral vectors.  Br J Urol. 1998;  81 (6) 870-874
  • 17 Chen L, Chen D, Block E, O'Donnell M, Kufe D W, Clinton S K. Eradication of murine bladder carcinoma by intratumor injection of a biscistronic adenoviral vector carrying cDNAs for the IL-12 heterodimer and its inhibition by the IL-12 p40 subunit homodimer.  J Immunol. 1997;  159 351-359
  • 18 Connor J, Bannerji R, Saito S, Heston W, Fair W, Gilboa E. Regression of bladder tumors in mice treated with interleukin 2 gene-modified tumor cells.  Exp Med. 1993;  177 (4) 1127-1134
  • 19 Horiguchi Y, Larchian W A, Kaplinsky R, Fair W R, Heston W D. Intravesical liposome-mediated interleukin-2 gene therapy in orthotopic murine bladder cancer model.  Gene Therapy. 2000;  7 (10) 844-851
  • 20 Yamanaka K, Hara I, Nagai H, Miyake H, Gohji K, Micallef M J, Kurimoto M, Arakawa S. Synergistic antitumor effects of interleukin-12 gene transfer and systemic administration of interleukin-18 in a mouse bladder cancer model.  Cancer Immunol Immunother. 1999;  48 (6) 297-302
  • 21 Milella M, Jacobelli J, Cavallo F, Guarini A, Velotti F, Frati L, Foa R, Forni G. Interleukin-2 gene transfer into human transitional cell carcinoma of the urinary bladder.  Br J Cancer. 1999;  79 (5 - 6) 770-779
  • 22 Garrido F, Ruiz-Cabello F. MHC expression of human tumors - its relevance for local tumor growth and metastasis.  Semin Cancer Biol. 1991;  2 (1) 3-10
  • 23 Saito S, Bannerji R, Gansbacher B, Rosenthal F M, Romanenko P, Heston W D, Fair W R, Gilboa E. Immunotherapy of bladder cancer with cytokine gene-modified tumor vaccines.  Cancer Res. 1994;  54 (13) 3516-3520
  • 24 Gueguen M, Patard J J, Gaugler B, Brasseur F, Renault J C, Van Cangh P J, Boon T, Van den Eynde B J. An antigen recognized by autologous CTLs on a human bladder carcinoma.  J Immunol. 1998;  160 (12) 6188-6194
  • 25 Moolten F L. Tumor chemosensitivity conferred by inserted herpes thymidine kinase genes: Paradigm for a prospective cancer control strategy.  Cancer Res. 1986;  46 (10) 5276-5281
  • 26 Sutton M A, Berkman S A, Chen S H, Block A, Dang T D, Kattan M W, Wheeler T M, Rowley D R. Adenovirus-mediated suicide gene therapy for experimental bladder cancer.  Urology. 1997;  49 (2) 173-180
  • 27 Mullen C A, Kilstrup M, Blaese R M. Transfer of the bacterial gene for cytosine deaminase to mammalian cells confers lethal sensitivity to 5-florocytosine: a negative selection system.  Proc Natl Acad Sci. 1992;  89 33-37
  • 28 Hughes B W, Wells A H, Bebok Z. Bystander killing of melanoma cells using the human tyrosinase promotor to express the Escherichia coli purine nucleoside phosphorylase gene.  Cancer Res. 1995;  55 3339-3345
  • 29 Freeman S M, Abboud C N, Whartenby K A, Packman C H, Koeplin D S, Moolten F L, Abraham G N. The „bystander effect”: tumor regression when a fraction of the tumor mass is genetically modified.  Cancer Res. 1993;  53 (21) 5274-5283
  • 30 Freije J M, MacDonald N J, Steeg P S. Nm 23 and tumour metastasis: a basic and translational advances.  Biochem Soc Symp. 1998;  63 261-271
  • 31 Huang Y W, Baluna R, Viretta E S. Adhesion molecules as targets for cancer therapy.  Histology and histopathology. 1997;  12 467-477
  • 32 Xu H J, Zhou Y, Seigne J, Perng G S, Mixon M, Zhang C, Li J, Benedict W F. Enhanced tumor suppressor gene therapy via replication-deficient protein. Adenovirus vectors expressing an N-terminal truncated retinoblastoma.  Cancer Res. 1996;  56 (10) 2245-2249
  • 33 Li J, Hu S X, Perng G S, Zhou Y, Xu K, Zhang C, Seigne J, Benedict W F, Xu H J. Expression of the retinoblastoma (RB) tumor suppressor gene inhibitis tumor cell invasion in vitro.  Oncogene. 1996;  13 (11) 2379-2386
  • 34 Feng M, Cabrera G, Deshane J, Scanlon K J, Curiel D T. Neoplastic reversion accomplished by high efficiency adenoviral-mediated delivery of an anti-ras ribozyme.  Cancer Res. 1995;  55 (10) 2024-2028
  • 35 Irie A, Anderegg B, Kashani-Sabet M, Ohkawa T, Suzuki T, Halks-Miller M, Curiel D T, Scanlon K J. Therapeutic efficacy of an adenovirus-mediated anti-H-ras ribozyme in experimental bladder cancer.  Antisense nucleic acid drug dev. 1999;  9 (4) 341-349
  • 36 Grim J, D'Amico A, Frizelle S, Zhou J, Kratzke R A, Curiel D T. Adenovirus-mediated delivery of p16 to p16-deficient human bladder cancer cells confers chemoresistance to cisplatin and paclitaxel.  Clin Cancer Res. 1997;  3 (12 Pt 1) 2415-2423
  • 37 Tanaka M, Sazawa A, Shinohara N, Kobayashi Y, Fujioka Y, Koyanagi T, Kuzumaki N. Gelsolin gene therapy by retrovirus producer cells for human bladder cancer in nude mice.  Cancer Gene Ther. 1999;  6 (5) 482-487
  • 38 Hall M C, Li Y, Pong R C, Ely B, Sagalowsky A I, Hsieh J T. The growth inhibitory effect of p21 adenovirus on human bladder cancer cells.  J Urol. 2000;  163 (3) 1033-1038
  • 39 Stein J P, Ginsberg D A, Grossfeld G D, Esrig D, Dickinson M G, Groshen S, Taylor C R, Skinner D G. The significance of p21 WAF1/CIP1 expression and tumor progression in bladder cancer.  J Urol. 1997;  157 (suppl) 161 A
  • 40 Koc O N, Allay J A, Lee K, Davis B M, Reese J S, Gerson S L. Transfer of drug resistance genes into hematopoietic progenitors to improve chemotherapy tolerance.  Semin Oncol. 1996;  23 (1) 46-65
  • 41 Sorrentino B P, Brand S J, Bodine D, Gottesman M, Pastan I, Cline A, Nienhuis A W. Selection of drug-resistant bone marrow cells in vivo after retroviral transfer of human MDR 1.  Science. 1992;  257 (5066) 99-103
  • 42 Cline M J. Gene transfer in intact animals.  Nature. 1980;  284 422-425
  • 43 Mercola K E, Stang H D, Browne J, Salser J, Cline M J. Insertion of a new gene of viral origin into bone marrow cells of mice.  Science. 1980;  208 1033-1035

Prof. Dr. med A Böhle

Klinik für Urologie Medizinische Universität zu Lübeck

Ratzeburger Allee 160 23538 Lübeck

Phone: Tel. +49-451-500-6112

Fax: Fax +49-451-500-6112

    >