Environmental Analysis Health and Toxicology

The Korean Society of Environmental Health and Toxicology (환경독성보건학회)
권호 표지

Toxicity of the Adenoviral Vector Mediated Gene Therapy

아데노바이러스 유전자치료제의 독성

  • Published : 2009.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

Adenoviral vector(AdV) has been the most widely used viral vector for delivering an exogenous therapeutic gene to human. As of this date, more clinical trials utilize recombinant AdV to treat cancer and monogenic inherited disease as well as vaccine applications. However, the number of clinical trials had dropped markedly following the tragic death of a patient ongoing an AdV therapy for the treatment of an ornithine transcarbamylase deficiency(OTCD). This review is an attempt to provide the information on toxicity generated by AdVmediated gene transfer. It would serve as a sobering reality to researchers and clinicians exploring the use of AdV, as to the complications involved in human application.

Keywords

References

  1. Bergelson JM, Cunningham JA, Droguett G, Kurt-Jones EA, Krithivas A, Hong JS, Horwitz MS, Crowell RL and Finberg RW. Isolation of a common receptor for cosackie B viruses and adenoviruses 2 and 5, Science 1997; 275 (5304): 1320-1323 https://doi.org/10.1126/science.275.5304.1320
  2. Boquet MP, Wonganan P, Dekker JD, Croyle MA. Influence of method of systemic administration of adenovirus on virusmediated toxicity: focus on mortality, virus distribution, and drug metabolism, J Pharmacol Toxicol Methods 2008; 58(3): 222-232 https://doi.org/10.1016/j.vascn.2008.07.003
  3. Dewey RA, Morrissey G, Cowsill CM, Stone D, Bolognani F, Dodd NJ, Southgate TD, Klatzmann D, Lassmann H, Castro MG and Lowenstein PR. Chronic brain inflammation and persistent herpes simplex virus 1 thymidine kinase expression in survivors of syngeneic glioma treated by adenovirus-mediated gene therapy: implications for clinical trials, Nat Med 1999; 5: 1256-1263 https://doi.org/10.1038/15207
  4. Dormond E, Perrier M and Kamen A. From the first to the third generation adenoviral vector: What parameters are governing the production yield? Biotechnol Advances 2009; 27(2): 133-144 https://doi.org/10.1016/j.biotechadv.2008.10.003
  5. Driesse MJ, Vincent AJ, Sillevis Smitt PA, Kros JM, Hoogerbrugge PM, Avezaat CJ, Valerio D and Bout A. Intracerebral injection of adenovirus harboring the HSVtk gene combined with ganciclovir administration: toxicity study in nonhuman primates, Gene Ther 1998; 5: 1122-1129 https://doi.org/10.1038/sj.gt.3300695
  6. Fechner H, Haack A, Wang H, Wang X, Eizema K, Pauschinger M, Schoemaker R, Veghel R, Houtsmuller A, Schultheiss HP, Lamers J and Poller W. Expression of coxsackie adenovirus receptor and alphav-integrin does not correlate with adenovector targeting in vivo indicating anatomical vector barriers, Gene Ther 1999; 6: 1520-1535 https://doi.org/10.1038/sj.gt.3301030
  7. Garcia-Banuelos J, Siller-Lopez F, Miranda A, Aguilar LK, Aguilar-Cordova E and Armendariz-Borunda J. Cirrhotic rat livers with extensive fibrosis can be safely transduced with clinical-grade adenoviral vectors. Evidence of cirrhosis reversion, Gene Ther 2002; 9: 127-134 https://doi.org/10.1038/sj.gt.3301647
  8. Gomez-Manzano C, Yung WK, Alemany R and Fueyo J. Genetically modified adenoviruses against gliomas: from bench to bedside, Neurol 2004; 63: 418-426 https://doi.org/10.1212/01.WNL.0000133302.15022.7F
  9. Krebs P, Scandella E, Odermatt B and Ludewig B. Rapid functional exhaustion and deletion of CTL following immunization with recombinant adenovirus, J Immunol 2005; 174: 4559-4566 https://doi.org/10.4049/jimmunol.174.8.4559
  10. Manickan E, Smith JS, Tian Jie, Eggerman TL, Lozier JN, Muller J and Byrnes AP. Rapid Kupffer cell death after intravenous injection of adenovirus vectors, Mol Ther 2006; 13(1): 108-117 https://doi.org/10.1016/j.ymthe.2005.08.007
  11. Markus JV, Vähä-Koskela B, Heikkilä JE and Hinkkanen AE. Oncolytic viruses in cancer therapy, Cancer Letters 2007; 254(2): 178-216 https://doi.org/10.1016/j.canlet.2007.02.002
  12. Massari I, Donnini A, Argentati K, Straino S, Mangoni A, Gaetano C, Viticchi C, Capogrossi M and Provinciali M. Age-dependent effects of repeated immunization with a first generation adenovirus vector on the immune response and transgene expression in young and old rats, Exp Gerontol 2002; 37: 823-831 https://doi.org/10.1016/S0531-5565(02)00011-6
  13. McConnell MJ and Imperiale MJ. Biology of adenovirus and its use as a vector for gene therapy, Human Gene Ther 2004; 15(11): 1022-1033 https://doi.org/10.1089/hum.2004.15.1022
  14. Morrissey RE, Horvath C, Snyder EA, Patrick J, Collins N, Evans E and MacDonald JS. Porcine toxicology studies of SCH 58500, an adenoviral vector for the p53 gene, Toxicol Sciences 2002a; 65(2): 256-265 https://doi.org/10.1093/toxsci/65.2.256
  15. Morrissey RE, Horvath C, Snyder EA, Patrick J and Mac- Donald JS. Rodent nonclinical safety evaluation studies of SCH 58500, an adenoviral vector for the p53 gene, Toxicol Sciences 2002b; 65(2): 266-275 https://doi.org/10.1093/toxsci/65.2.266
  16. Pearson S, Jia H and Kandachi K. China approves first gene therapy. Nat Biotechnol 2004; 22(1): 3-4 https://doi.org/10.1038/nbt0104-3
  17. Raki M, Kanerva A, Ristimaki A, Desmond RA, Chen TD, Ranki T, Sarkioja M, Kangasniemi L and Hemminki A. Combination of gemcitabine and Ad5/3-Delta24, a tropism modified conditionally replicating adenovirus, for the treatment of ovarian cancer, Gene Ther 2005; 12: 1198-1205 https://doi.org/10.1038/sj.gt.3302517
  18. Raper SE, Yudkoff M, Chirmule N, Gao GP, Nunes F, Haskal ZJ, Furth EE, Propert KJ, Robinson MB, Magosin S, Simoes H, Speicher L, Hughes J, Tazelaar J, Wivel NA, Wilson JM and Batshaw ML. A pilot study of in vivo liver-directed gene transfer with an adenoviral vector in partial ornithine transcarbamylase deficiency. Human Gene Ther 2002; 13(1): 163-175 https://doi.org/10.1089/10430340152712719
  19. Raper SE, Chirmule N, Lee FS, Wivel NA, Bagg A, Gao G, Wilson JM and Batshaw ML. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer, Mol Genet Met 2003; 80(1-2): 148-158 https://doi.org/10.1016/j.ymgme.2003.08.016
  20. Raper SE. Gene therapy: The good, the bad, and the ugly, Surgery 2005; 137(5): 487-492 https://doi.org/10.1016/j.surg.2004.10.014
  21. Su C, Cao H, Tan S, Huang Y, Jia X JL, Wang K, Chen Y, Long J, Liu X, Wu M, Wu X and Qian Q. Toxicology profiles of a novel p53-armed replication-competent oncolytic adenovirus in rodents, felids, and nonhuman primates, Toxicol Sciences 2008; 106(1): 242-250 https://doi.org/10.1093/toxsci/kfn168
  22. Thomas CE, Birkett D, Anozie I, Castro MG and Lowenstein PR. Acute direct adenoviral vector cytotoxicity and chronic, but not acute, inflammatory responses correlate with decreased vector-mediated transgene expression in the brain, Mol Ther 2001; 3(1): 36-46 https://doi.org/10.1006/mthe.2000.0224
  23. Tripathy SK, Goldwasser MM, Lu EB and Leiden JM. Stable delivery of physiologic levels of recombinant erythropoietin to the systemic circulation by intramuscular injection of replication-defective adenovirus, Proc Natl Acad Sci USA 1994; 91: 11557-11561 https://doi.org/10.1073/pnas.91.24.11557
  24. Vlachaki MT, Hernandez-Garcia A, Ittmann M, Chhikara M, Aguilar LK, Zhu X, The BS, Butler EB, Woo S, Thompson TC, Barrera-Saldana H and guilar-Cordova E. Impact of preimmunization on adenoviral vector expression and toxicity in a subcutaneous mouse cancer model, Mol Ther 2002; 6: 342-348 https://doi.org/10.1006/mthe.2002.0669
  25. Wickham TJ, Mathias P, Cheresh DA and Nemerow G. Integrins ${\alpha}v{\beta}3$ and ${\alpha}v{\beta}5$ promote adenovirus internalization but not virus attachment, Cell 1993; 73: 309-319 https://doi.org/10.1016/0092-8674(93)90231-E
  26. Zhang Y, Chirmule N, Gao GP, Qian R, Croyle M, Joshi B, Tazelaar J and Wilson JM. Acute cytokine response to systemic adenoviral vectors in mice is mediated by dendritic cells and macrophages, Mol Ther 2001; 3(51): 697-707 https://doi.org/10.1006/mthe.2001.0329