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Efficacy, Toxicity, and Immunogenicity of Adenoviral Vectors

  • Chapter
Gene Therapy for Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

To date, over 60% of all gene therapy clinical trials in the United States have focused on the development and validation of new therapies for cancer. Many of these trials utilize Ad vectors as novel anticancer therapeutics. In recent years, however, initial enthusiasm and high expectations for successful clinical application of Ad-based vectors as efficient anticancer therapeutics has been dampened based on the data obtained during a series of clinical trials. Along with the major concerns over the safety of systemic Ad application, which was found to be associated with immediate innate and inflammatory host responses and can also lead to fatalities, such issues as rapid clearance of the bulk of administered vector by cells of the reticulo-endothelial system, neutralization of virus particles by highly prevalent pre-existing antibodies, and poor transduction of primary tumors resulting from low-level Ad receptor expression and/or anatomical barriers, including extracellular matrix surrounding tumors, have established a great need for research to further improve existing Ad vectors and unravel their true therapeutic potential as anticancer agents. This chapter reviews and discusses the current status, limitations and future challenges for the Ad vector development field with respect to their efficacy, toxicity and immunogenicity.

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References

  1. Journal of Gene Medicine website, http://www.wiley.co.uk/genmed/clinical/.

  2. Brunetti-Pierri N, Palmer DJ, Beaudet AL, Carey KD, Finegold M, Ng P. Acute toxicity after highdose systemic injection of helper-dependent adenoviral vectors into nonhuman primates. Hum Gene Ther 2004;15:35–46.

    Article  PubMed  CAS  Google Scholar 

  3. Nunes FA, Furth EE, Wilson JM, Raper SE. Gene transfer into the liver of nonhuman primates with El-deleted recombinant adenoviral vectors: safety of readministration. Hum Gene Ther 1999; 10:2515–2526.

    Article  PubMed  CAS  Google Scholar 

  4. Huebner RJ, Rowe WP, Schatten WE, Smith RR, Thomas LB. Studies on the use of viruses in the treatment of carcinoma of the cervix. Cancer 1956;9:1211–1218.

    Article  PubMed  CAS  Google Scholar 

  5. Kirn D, Martuza RL, Zwiebel J. Replication-selective virotherapy for cancer: Biological principles, risk management and future directions. Nat Med 2001;7:781–787.

    Article  PubMed  CAS  Google Scholar 

  6. McCormick F. Cancer gene therapy: fringe or cutting edge? Nat Rev Cancer 2001;1: 130–141.

    Article  PubMed  CAS  Google Scholar 

  7. Roth JA, Cristiano RJ. Gene therapy for cancer: what have we done and where are we going? J Natl Cancer Inst 1997;89:21–39.

    Article  PubMed  CAS  Google Scholar 

  8. Qiao J, Doubrovin M, Sauter BV, et al. Tumor-specific transcriptional targeting of suicide gene therapy. Gene Ther 2002;9:168–175.

    Article  PubMed  CAS  Google Scholar 

  9. Bischoff JR, Kirn DH, Williams A, et al. An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science 1996;274:373–376.

    Article  PubMed  CAS  Google Scholar 

  10. Heise C, Sampson-Johannes A, Williams A, McCormick F, Von Hoff DD, Kirn DH. ONYX-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherapeutic agents. Nat Med 1997;3:639–645.

    Article  PubMed  CAS  Google Scholar 

  11. Heise CC, Williams AM, Xue S, Propst M, Kirn DH. Intravenous administration of ONYX-015, a selectively replicating adenovirus, induces antitumoral efficacy. Cancer Res 1999;59:2623–2628.

    PubMed  CAS  Google Scholar 

  12. Heise CC, Williams A, Olesch J, Kirn DH. Efficacy of a replication-competent adenovirus (ONYX-015) following intratumoral injection: intratumoral spread and distribution effects. Cancer Gene Ther 1999;6:499–504.

    Article  PubMed  CAS  Google Scholar 

  13. Kirn D. Clinical research results with dl1520 (Onyx-015), a replication-selective adenovirus for the treatment of cancer: what have we learned? Gene Ther 2001;8:89–98.

    Article  PubMed  CAS  Google Scholar 

  14. Reid T, Galanis E, Abbruzzese J, et al. Hepatic arterial infusion of a replication-selective oncolytic adenovirus (dl1520): phase II viral, immunologic, and clinical endpoints. Cancer Res 2002; 62:6070–6079.

    PubMed  CAS  Google Scholar 

  15. Nemunaitis J, Cunningham C, Buchanan A, et al. Intravenous infusion of a replication-selective adenovirus (ONYX-015) in cancer patients: safety, feasibility and biological activity. Gene Ther 2001; 8:746–759.

    Article  PubMed  CAS  Google Scholar 

  16. Nemunaitis J, Khuri F, Ganly I, et al. Phase II trial of intratumoral administration of ONYX-015, a replication-selective adenovirus, in patients with refractory head and neck cancer. J Clin Oncol 2001; 19:289–298.

    PubMed  CAS  Google Scholar 

  17. Huang J, Bai YX, Han SW, et al. A human TERT C-terminal polypeptide sensitizes HeLa cells to H2O2-induced senescence without affecting telomerase enzymatic activity. Biochem Biophys Res Commun 2003;301:627–632.

    Article  PubMed  CAS  Google Scholar 

  18. Yu DC, Sakamoto GT, Henderson DR. Identification of the transcriptional regulatory sequences of human kallikrein 2 and their use in the construction of calydon virus 764, an attenuated replication competent adenovirus for prostate cancer therapy. Cancer Res 1999;59:1498–1504.

    PubMed  CAS  Google Scholar 

  19. Hallenbeck PL, Chang YN, Hay C, et al. A novel tumor-specific replication-restricted adenoviral vector for gene therapy of hepatocellular carcinoma. Hum Gene Ther 1999;10:1721–1733.

    Article  PubMed  CAS  Google Scholar 

  20. Li Y, Yu DC, Chen Y, et al. A hepatocellular carcinoma-specific adenovirus variant, CV890, eliminates distant human liver tumors in combination with doxorubicin. Cancer Res 2001;61:6428–6436.

    PubMed  CAS  Google Scholar 

  21. Yu DC, Chen Y, Seng M, Dilley J, Henderson DR. The addition of adenovirus type 5 region E3 enables calydon virus 787 to eliminate distant prostate tumor xenografts. Cancer Res 1999; 59:4200–4203.

    PubMed  CAS  Google Scholar 

  22. Rodriguez R, Schuur ER, Lim HY, Henderson GA, Simons JW, Henderson DR. Prostate attenuated replication competent adenovirus (ARCA) CN706: a selective cytotoxic for prostate-specific antigen-positive prostate cancer cells. Cancer Res 1997;57:2559–2563.

    PubMed  CAS  Google Scholar 

  23. Post DE, Khuri FR, Simons JW, Van Meir EG. Replicative oncolytic adenoviruses in multimodal cancer regimens. Hum Gene Ther 2003; 14:933–946.

    Article  PubMed  CAS  Google Scholar 

  24. Rasmussen H, Rasmussen C, Lempicki M, et al. TNFerade Biologic: preclinical toxicology of a novel adenovector with a radiation-inducible promoter, carrying the human tumor necrosis factor alpha gene. Cancer Gene Ther 2002;9:951–957.

    Article  PubMed  CAS  Google Scholar 

  25. Steinwaerder DS, Carlson CA, Otto DL, Li ZY, Ni S, Lieber A. Tumor-specific gene expression in hepatic metastases by a replication-activated adenovirus vector. Nat Med 2001;7:240–243.

    Article  PubMed  CAS  Google Scholar 

  26. Fueyo J, Alemany R, Gomez-Manzano C, et al. Preclinical characterization of the antiglioma activity of a tropism-enhanced adenovirus targeted to the retinoblastoma pathway. J Natl Cancer Inst 2003;95:652–660.

    Article  PubMed  CAS  Google Scholar 

  27. Reid T, Warren R, Kirn D. Intravascular adenoviral agents in cancer patients: lessons from clinical trials. Cancer Gene Ther 2002;9:979–986.

    Article  PubMed  CAS  Google Scholar 

  28. Hermiston TW, Kuhn I. Armed therapeutic viruses: strategies and challenges to arming oncolytic viruses with therapeutic genes. Cancer Gene Ther 2002;9:1022–1035.

    Article  PubMed  CAS  Google Scholar 

  29. Bauzon M, Castro D, Karr M, Hawkins LK, Hermiston TW. Multigene expression from a replicating adenovirus using native viral promoters. Mol Ther 2003;7:526–534.

    Article  PubMed  CAS  Google Scholar 

  30. DeWeese TL, van der Poel H, Li S, et al. A phase I trial of CV706, a replication-competent, PSA selective oncolytic adenovirus, for the treatment of locally recurrent prostate cancer following radiation therapy. Cancer Res 2001;61:7464–7472.

    PubMed  CAS  Google Scholar 

  31. Doronin K, Toth K, Kuppuswamy M, WardT P, Tollefson AE, Wold WS. Tumor-specific, replicationcompetent adenovirus vectors overexpressing the adenovirus death protein. J Virol 2000; 74:6147–6155.

    Article  PubMed  CAS  Google Scholar 

  32. Doronin K, Toth K, Kuppuswamy M, Krajcsi P, Tollefson AE, Wold WS. Overexpression of the ADP (E3-11.6K) protein increases cell lysis and spread of adenovirus. Virology 2003;305:378–387.

    Article  PubMed  CAS  Google Scholar 

  33. Doronin K, Kuppuswamy M, Toth K, et al. Tissue-specific, tumor-selective, replication-competent adenovirus vector for cancer gene therapy. J Virol 2001;75:3314–3324.

    Article  PubMed  CAS  Google Scholar 

  34. Mi J, Li ZY, Ni S, Steinwaerder D, Lieber A. Induced apoptosis supports spread of adenovirus vectors in tumors. Hum Gene Ther 2001;12:1343–1352.

    Article  PubMed  CAS  Google Scholar 

  35. Yoshida Y, Sadata A, Zhang W, Saito K, Shinoura N, Hamada H. Generation of fiber-mutant recombinant adenoviruses for gene therapy of malignant glioma. Hum Gene Ther 1998;9:2503–2515.

    Article  PubMed  CAS  Google Scholar 

  36. Shinoura N, Yoshida Y, Tsunoda R, et al. Highly augmented cytopathic effect of a fiber-mutant E1B-defective adenovirus for gene therapy of gliomas. Cancer Res 1999;59:3411–346.

    PubMed  CAS  Google Scholar 

  37. Volk AL, Rivera AA, Kanerva A, et al. Enhanced adenovirus infection of melanoma cells by fiber-modification: incorporation of RGD peptide or Ad5/3 chimerism. Cancer Biol Ther 2003;2:511–515.

    PubMed  CAS  Google Scholar 

  38. Dehari H, Ito Y, Nakamura T, et al. Enhanced antitumor effect of RGD fiber-modified adenovirus for gene therapy of oral cancer. Cancer Gene Ther 2003; 10:75–85.

    Article  PubMed  CAS  Google Scholar 

  39. Nagel H, Maag S, Tassis A, Nestle FO, Greber UF, Hemmi S. The alphavbeta5 integrin of hematopoietic and nonhematopoietic cells is a transduction receptor of RGD-4C fiber-modified adenoviruses. Gene Ther 2003; 10:1643–1653.

    Article  PubMed  CAS  Google Scholar 

  40. Suzuki K, Fueyo J, Krasnykh V, Reynolds PN, Curiel DT, Alemany R. A conditionally replicative adenovirus with enhanced infectivity shows improved oncolytic potency. Clin Cancer Res 2001; 7:120–126.

    PubMed  CAS  Google Scholar 

  41. Bauerschmitz GJ, Lam JT, Kanerva A, et al. Treatment of ovarian cancer with a tropism modified oncolytic adenovirus. Cancer Res 2002;62:1266–1270.

    PubMed  CAS  Google Scholar 

  42. Raper SE, Chirmule N, Lee FS, et al. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol Genet Metab 2003; 80:148–158.

    Article  PubMed  CAS  Google Scholar 

  43. Wein LM, Wu JT, Kirn DH. Validation and analysis of a mathematical model of a replication-competent oncolytic virus for cancer treatment: implications for virus design and delivery. Cancer Res 2003;63:1317–1324.

    PubMed  CAS  Google Scholar 

  44. Demers GW, Johnson DE, Tsai V, et al. Pharmacologic indicators of antitumor efficacy for oncolytic virotherapy. Cancer Res 2003;63:4003–4008.

    PubMed  CAS  Google Scholar 

  45. Nemerow GR. Cell receptors involved in adenovirus entry. Virology 2000;274: 1–4.

    Article  PubMed  CAS  Google Scholar 

  46. Bergelson JM. Receptors mediating adenovirus attachment and internalization. Biochem Pharmacol 1999;57:975–979.

    Article  PubMed  CAS  Google Scholar 

  47. Meier O, Greber UF. Adenovirus endocytosis. J Gene Med 2003;5:451–462.

    Article  PubMed  CAS  Google Scholar 

  48. Roelvink PW, Lizonova A, Lee JG, et al. The coxsackievirus-adenovirus receptor protein can function as a cellular attachment protein for adenovirus serotypes from subgroups A, C, D, E, and F. J Virol 1998;72:7909–7915.

    PubMed  CAS  Google Scholar 

  49. Roelvink PW, Mi Lee G, Einfeld DA, Kovesdi I, Wickham TJ. Identification of a conserved receptorbinding site on the fiber proteins of CAR-recognizing adenoviridae. Science 1999;286:1568–1571.

    Article  PubMed  CAS  Google Scholar 

  50. Bergelson JM, Cunningham JA, Droguett G, et al. Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science 1997;275:1320–1323.

    Article  PubMed  CAS  Google Scholar 

  51. Tomko RP, Xu R, Philipson L. HCAR and MCAR: the human and mouse cellular receptors for subgroup C adenoviruses and group B coxsackieviruses. Proc Natl Acad Sci U S A 1997;94:3352–3356.

    Article  PubMed  CAS  Google Scholar 

  52. Gaggar A, Shayaklumetov DM, Lieber A. CD46 is a cellular receptor for group B adenoviruses. Nature Medicine 2003;9:1408–1412.

    Article  PubMed  CAS  Google Scholar 

  53. Segerman A, Atkinson JP, Marttila M, Dennerquist V, Wadell G, Arnberg N. Adenovirus type 11 uses CD46 as a cellular receptor. J Virol 2003;77:9183–9191.

    Article  PubMed  CAS  Google Scholar 

  54. Wang X, Bergelson JM. Coxsackievirus and adenovirus receptor cytoplasmic and transmembrane domains are not essential for coxsackievirus and adenovirus infection. J Virol 1999;73:2559–2562.

    PubMed  CAS  Google Scholar 

  55. Wickham TJ, Mathias P, Cheresh DA, Nemerow GR. Integrins alpha v beta 3 and alpha v beta 5 promote adenovirus internalization but not virus attachment. Cell 1993;73:309–319.

    Article  PubMed  CAS  Google Scholar 

  56. Li E, Brown SL, Stupack DG, Puente XS, Cheresh DA, Nemerow GR. Integrin alpha(v)betal is an adenovirus coreceptor. J Virol 2001;75:5405–5409.

    Article  PubMed  CAS  Google Scholar 

  57. Davison E, Diaz RM, Hart IR, Santis G, Marshall JF Integrin alpha5beta1-mediated adenovirus infection is enhanced by the integrin-activating antibody TS2/16. J Virol 1997;71:6204–6207.

    PubMed  CAS  Google Scholar 

  58. Davison E, Kirby I, Whitehouse J, Hart I, Marshall JF, Santis G. Adenovirus type 5 uptake by lung adenocarcinoma cells in culture correlates with Ad5 fibre binding is mediated by alpha(v)betal integrin and can be modulated by changes in beta1 integrin function. J Gene Med 2001;3:550–559.

    Article  PubMed  CAS  Google Scholar 

  59. Huang S, Kamata T, Takada Y, Ruggeri ZM, Nemerow GR. Adenovirus interaction with distinct integrins mediates separate events in cell entry and gene delivery to hematopoietic cells. J Virol 1996;70:4502–4508.

    PubMed  CAS  Google Scholar 

  60. Liu Q, Muruve DA. Molecular basis of the inflammatory response to adenovirus vectors. Gene Ther 2003; 10:935–940.

    Article  PubMed  CAS  Google Scholar 

  61. Li E, Stupack D, Klemke R, Cheresh DA, Nemerow GR. Adenovirus endocytosis via alpha(v) integrins requires phosphoinositide-3-OH kinase. J Virol 1998;72:2055–2061.

    PubMed  CAS  Google Scholar 

  62. Li E, Stupack D, Bokoch GM, Nemerow GR. Adenovirus endocytosis requires actin cytoskeleton reorganization mediated by Rho family GTPases. J Virol 1998;72:8806–8812.

    PubMed  CAS  Google Scholar 

  63. Suomalainen M, Nakano MY, Boucke K, Keller S, Greber UF. Adenovirus-activated PKA and p38/MAPK pathways boost microtubule-mediated nuclear targeting of virus. Embo J 2001;20:1310–1319.

    Article  PubMed  CAS  Google Scholar 

  64. Bhat NR, Fan F. Adenovirus infection induces microglial activation: involvement of mitogen-activated protein kinase pathways. Brain Res 2002;948:93–101.

    Article  PubMed  CAS  Google Scholar 

  65. Nemerow GR, Stewart PL. Role of alpha(v) integrins in adenovirus cell entry and gene delivery. Microbiol Mol Biol Rev 1999;63:725–734.

    PubMed  CAS  Google Scholar 

  66. Li E, Stupack DG, Brown SL, Klemke R, Schlaepfer DD, Nemerow GR. Association of p130CAS with phosphatidylinositol-3-OH kinase mediates adenovirus cell entry. J Biol Chem 2000; 275:14,729–14,735.

    CAS  Google Scholar 

  67. Tibbies LA, Spurrell JC, Bowen GP, et al. Activation of p38 and ERK signaling during adenovirus vector cell entry lead to expression of the C-X-C chemokine IP-10. J Virol 2002;76:1559–1568.

    Article  CAS  Google Scholar 

  68. Bruder JT, Kovesdi I. Adenovirus infection stimulates the Raf/MAPK signaling pathway and induces interleukin-8 expression. J Virol 1997;71:398–404.

    PubMed  CAS  Google Scholar 

  69. Bowen GP, Borgland SL, Lam M, Libermann TA, Wong NC, Muruve DA. Adenovirus vector-induced inflammation: capsid-dependent induction of the C-C chemokine RANTES requires NF-kappa B. Hum Gene Ther 2002;13:367–379.

    Article  PubMed  CAS  Google Scholar 

  70. Borgland SL, Bowen GP, Wong NC, Libermann TA, Muruve DA. Adenovirus vector-induced expression of the C-X-C chemokine IP-10 is mediated through capsid-dependent activation of NF-kappaB. J Virol 2000;74:3941–3947.

    Article  PubMed  CAS  Google Scholar 

  71. Tamanini A, Rolfini R, Nicolis E, Melotti P, Cabrini G. MAP kinases and NF-kappaB collaborate to induce ICAM-1 gene expression in the early phase of adenovirus infection. Virology 2003;307: 228–242.

    Article  PubMed  CAS  Google Scholar 

  72. Suomalainen M, Nakano MY, Keller S, Boucke K, Stidwill RP, Greber UF. Microtubule-dependent plus-and minus end-directed motilities are competing processes for nuclear targeting of adenovirus. J Cell Biol 1999;144:657–672.

    Article  PubMed  CAS  Google Scholar 

  73. Mabit H, Nakano MY, Prank U, et al. Intact microtubules support adenovirus and herpes simplex virus infections. J Virol 2002;76:9962–9971.

    Article  PubMed  CAS  Google Scholar 

  74. Wang K, Guan T, Cheresh DA, Nemerow GR. Regulation of adenovirus membrane penetration by the cytoplasmic tail of integrin beta5. J Virol 2000;74:2731–2739.

    Article  PubMed  CAS  Google Scholar 

  75. Brakebusch C, Fassler R. The integrin-actin connection, an eternal love affair. Embo J 2003; 22:2324–2333.

    Article  PubMed  CAS  Google Scholar 

  76. Yurochko AD, Liu DY, Eierman D, Haskill S. Integrins as a primary signal transduction molecule regulating monocyte immediate-early gene induction. Proc Natl Acad Sci U S A 1992;89:9034–9038.

    Article  PubMed  CAS  Google Scholar 

  77. Ritzenthaler JD, Roman J. Interleukin-1beta gene transcription in U937 cells is modulated by type I collagen and cytoskeletal integrity via distinct signaling pathways. J Interferon Cytokine Res 2001; 21:105–116.

    Article  PubMed  CAS  Google Scholar 

  78. Roman J, Ritzenthaler JD, PerezT RL, Roser SL. Differential modes of regulation of interleukin-1beta expression by extracellular matrices. Immunology 1999;98:228–237.

    Article  PubMed  CAS  Google Scholar 

  79. Roman J, Ritzenthaler JD, Fenton MJ, Roser S, Schuyler W. Transcriptional regulation of the human interleukin 1beta gene by fibronectin: role of protein kinase C and activator protein 1 (AP-1). Cytokine 2000; 12:1581–1596.

    Article  PubMed  CAS  Google Scholar 

  80. Mizuguchi H, Koizumi N, Hosono T, et al. CAR-or alphav integrin-binding ablated adenovirus vectors, but not fiber-modified vectors containing RGD peptide, do not change the systemic gene transfer properties in mice. Gene Ther 2002;9:769–776.

    Article  PubMed  CAS  Google Scholar 

  81. Akiyama M, Roelvink P, Einfeld D, Kovesdi I, King CR. Effect of Ablating CAR and integrin binding on the biodistribution and cellular localization of adenovirus vectors following intravenous or intraperitO’Neal delivery. Mol Ther 2003;7(5):S173.

    Google Scholar 

  82. Alemany R, Curiel DT. CAR-binding ablation does not change biodistribution and toxicity of adenoviral vectors. Gene Ther 2001;8:1347–1353.

    Article  PubMed  CAS  Google Scholar 

  83. Fechner H, Haack A, Wang H, et al. 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.

    Article  PubMed  CAS  Google Scholar 

  84. Smith T, Idamakanti N, Kylefjord H, et al. In vivo hepatic adenoviral gene delivery occurs independently of the coxsackievirus-adenovirus receptor. Mol Ther 2002;5:770–779.

    Article  PubMed  CAS  Google Scholar 

  85. Dechecchi MC, Melotti P, Bonizzato A, Santacatterina M, Chilosi M, Cabrini G. Heparan sulfate glycosaminoglycans are receptors sufficient to mediate the initial binding of adenovirus types 2 and 5. J Virol 2001;75:8772–8780.

    Article  PubMed  CAS  Google Scholar 

  86. Balakireva L, Schoehn G, Thouvenin E, Chroboczek J. Binding of adenovirus capsid to dipalmitoyl phosphatidylcholine provides a novel pathway for virus entry. J Virol 2003;77:4858–4866.

    Article  PubMed  CAS  Google Scholar 

  87. Hautala T, Grunst T, Fabrega A, Freimuth P, Welsh MJ. An interaction between penton base and alpha v integrins plays a minimal role in adenovirus-mediated gene transfer to hepatocytes in vitro and in vivo. Gene Ther 1998;5:1259–1264.

    Article  PubMed  CAS  Google Scholar 

  88. Alemany R, Suzuki K, Curiel DT. Blood clearance rates of adenovirus type 5 in mice. J Gen Virol 2000;81:2605–269.

    PubMed  CAS  Google Scholar 

  89. Tao N, Gao GP, Parr M, et al. Sequestration of adenoviral vector by Kupffer cells leads to a nonlinear dose response of transduction in liver. Mol Ther 2001;3:28–35.

    Article  PubMed  CAS  Google Scholar 

  90. Worgall S, Wolff G, Falck-Pedersen E, Crystal RG. Innate immune mechanisms dominate elimination of adenoviral vectors following in vivo administration. Hum Gene Ther 1997;8:37–44.

    PubMed  CAS  Google Scholar 

  91. Raper SE, Yudkoff M, Chirmule N, et al. A pilot study of in vivo liver-directed gene transfer with an adenoviral vector in partial ornithine transcarbamylase deficiency. Hum Gene Ther 2002; 13:163–175.

    Article  PubMed  CAS  Google Scholar 

  92. Assessment of adenoviral vector safety and toxicity: Report of the National Institutes of Health Recombinant DNA Advisory Committee. Hum Gene Ther 2002;13:3–13.

    Google Scholar 

  93. Lozier JN, Csako G, Mondoro TH, et al. Toxicity of a first-generation adenoviral vector in rhesus macaques. Hum Gene Ther 2002; 13:113–124.

    Article  PubMed  CAS  Google Scholar 

  94. Morral N, O’Neal WK, Rice K, et al. Lethal toxicity, severe endothelial injury, and a threshold effect with high doses of an adenoviral vector in baboons. Hum Gene Ther 2002; 13:143–154.

    Article  PubMed  CAS  Google Scholar 

  95. Schnell MA, Zhang Y, Tazelaar J, et al. Activation of innate immunity in nonhuman primates following intraportal administration of adenoviral vectors. Mol Ther 2001;3:708–722.

    Article  PubMed  CAS  Google Scholar 

  96. Lieber A, He CY, Meuse L, et al. The role of Kupffer cell activation and viral gene expression in early liver toxicity after infusion of recombinant adenovirus vectors. J Virol 1997;71:8798–8807.

    PubMed  CAS  Google Scholar 

  97. Schiedner G, Hertel S, Johnston M, Dries V, van Rooijen N, Kochanek S. Selective depletion or blockade of Kupffer cells leads to enhanced and prolonged hepatic transgene expression using highcapacity adenoviral vectors. Mol Ther 2003;7:35–43.

    Article  PubMed  CAS  Google Scholar 

  98. Vigne E, Dedieu JF, Brie A, et al. Genetic manipulations of adenovirus type 5 fiber resulting in liver tropism attenuation. Gene Ther 2003;10:153–162.

    Article  PubMed  CAS  Google Scholar 

  99. Smith TA, Idamakanti N, Rollence ML, et al. Adenovirus serotype 5 fiber shaft influences in vivo gene transfer in mice. Hum Gene Ther 2003; 14:777–787.

    Article  PubMed  CAS  Google Scholar 

  100. Shayakhmetov D. M. Z-YL, S. Ni, A Lieber. Analysis of adenovirus sequestration in the liver, transduction of hepatic cells, and innate toxicity after injection of fiber-modified vectors. J Virol 2004; 78:5368–5381.

    Article  PubMed  CAS  Google Scholar 

  101. Shayakhmetov DM, Gaggar A, Ni S, Li ZY, Lieber A. Adenovirus binding to blood factors results in liver cell infection and hepatotoxicity. J Virol 2005;79:7478–7491.

    Article  PubMed  CAS  Google Scholar 

  102. Ruuskanen O MO, Akusjarvi G. Adenoviruses. 2002:515–534.

    Google Scholar 

  103. Shenk T. Adenoviridae. in Field’s Virology (D.M. Nipe and RM. Howley, Eds.) 2001:2265–2328.

    Google Scholar 

  104. Kojaoghlanian T, Flomenberg R Horwitz MS. The impact of adenovirus infection on the immunocompromised host. Rev Med Virol 2003;13:155–171.

    Article  PubMed  Google Scholar 

  105. Mahanty S, Hutchinson K, Agarwal S, McRae M, Rollin PE, Pulendran B. Cutting edge: impairment of dendritic cells and adaptive immunity by Ebola and Lassa viruses. J Immunol 2003;170: 2797–2801.

    PubMed  CAS  Google Scholar 

  106. Benedict CA, Norris PS, Ware CF. To kill or be killed: viral evasion of apoptosis. Nat Immunol 2002;3:1013–1018.

    Article  PubMed  CAS  Google Scholar 

  107. Benedict CA, Banks TA, Ware CF. Death and survival: viral regulation of TNF signaling pathways. Curr Opin Immunol 2003; 15:59–65.

    Article  PubMed  CAS  Google Scholar 

  108. Wold WS, Doronin K, Toth K, Kuppuswamy M, Lichtenstein DL, Tollefson AE. Immune responses to adenoviruses: viral evasion mechanisms and their implications for the clinic. Curr Opin Immunol 1999;11:380–386.

    Article  PubMed  CAS  Google Scholar 

  109. Yasuda M, Theodorakis P. Subramanian T, Chinnadurai G. Adenovirus E1B-19K/BCL-2 interacting protein BNIR3 contains a BH3 domain and a mitochondrial targeting sequence. J Biol Chem 1998; 273:12, 415–412, 421.

    Google Scholar 

  110. Martin ME, Berk AJ. Adenovirus E1B 55K represses p53 activation in vitro. J Virol 1998; 72:3146–3154.

    PubMed  CAS  Google Scholar 

  111. Leonard GT, Sen GC. Effects of adenovirus E1A protein on interferon-signaling. Virology 1996; 224:25–33.

    Article  PubMed  CAS  Google Scholar 

  112. Mathews MB, Shenk T. Adenovirus virus-associated RNA and translation control. J Virol 1991; 65:5657–5662.

    PubMed  CAS  Google Scholar 

  113. Feuerbach D, Etteldorf S, Ebenau-Jehle C, Abastado JR Madden D, Burgert HG. Identification of amino acids within the MHC molecule important for the interaction with the adenovirus protein E3/19K. J Immunol 1994;153:1626–1636.

    PubMed  CAS  Google Scholar 

  114. Beier DC, Cox JH, Vining DR, Cresswell R Engelhard VH. Association of human class I MHC alleles with the adenovirus E3/19K protein. J Immunol 1994;152:3862–3872.

    PubMed  CAS  Google Scholar 

  115. Benedict CA, Norris PS, Prigozy TI, et al. Three adenovirus E3 proteins cooperate to evade apoptosis by tumor necrosis factor-related apoptosis-inducing ligand receptor-1 and-2. J Biol Chem 2001; 276:3270–3278.

    Article  PubMed  CAS  Google Scholar 

  116. Tollefson AE, Hermiston TW, Lichtenstein DL, et al. Forced degradation of Fas inhibits apoptosis in adenovirus-infected cells. Nature 1998;392:726–730.

    Article  PubMed  CAS  Google Scholar 

  117. Mistchenko AS, Diez RA, Mariani AL, et al. Cytokines in adenoviral disease in children: association of interleukin-6, interleukin-8, and tumor necrosis factor alpha levels with clinical outcome. J Pediatr 1994;124:714–720.

    Article  PubMed  CAS  Google Scholar 

  118. Ginsberg HS, Prince GA. The molecular basis of adenovirus pathogenesis. Infect Agents Dis 1994; 3:1–8.

    PubMed  CAS  Google Scholar 

  119. Prince GA, Porter DD, Jenson AB, Horswood RL, Chanock RM, Ginsberg HS. Pathogenesis of adenovirus type 5 pneumonia in cotton rats (Sigmodon hispidus). J Virol 1993;67:101–111.

    PubMed  CAS  Google Scholar 

  120. Garnett CT, Erdman D, Xu W, Gooding LR. Prevalence and quantitation of species C adenovirus DNA in human mucosal lymphocytes. J Virol 2002;76:10,608–10,616.

    Article  CAS  Google Scholar 

  121. Croyle MA, Chirmule N, Zhang Y, Wilson JM. PEGylation of E1-deleted adenovirus vectors allows significant gene expression on readministration to liver. Hum Gene Ther 2002; 13:1887–1900.

    Article  PubMed  CAS  Google Scholar 

  122. O’Riordan CR, Lachapelle A, Delgado C, et al. PEGylation of adenovirus with retention of infectivity and protection from neutralizing antibody in vitro and in vivo. Hum Gene Ther 1999; 10: 1349–1358.

    Article  PubMed  CAS  Google Scholar 

  123. Nwanegbo E, Vardas E, Gao W, et al. Prevalence of neutralizing antibodies to adenoviral serotypes 5 and 35 in the adult populations of The Gambia, South Africa, and the United States. Clin Diagn Lab Immunol 2004;11:351–357.

    Article  PubMed  CAS  Google Scholar 

  124. Sakurai F, Mizuguchi H, Yamaguchi T, Hayakawa T. Characterization of in vitro and in vivo gene transfer properties of adenovirus serotype 35 vector. Mol Ther 2003;8:813–821.

    Article  PubMed  CAS  Google Scholar 

  125. Vogels R, Zuijdgeest D, van Rijnsoever R, et al. Replication-deficient human adenovirus type 35 vectors for gene transfer and vaccination: efficient human cell infection and bypass of preexisting adenovirus immunity. J Virol 2003;77:8263–8271.

    Article  PubMed  CAS  Google Scholar 

  126. Hemminki A, Kanerva A, Kremer EJ, et al. A canine conditionally replicating adenovirus for evaluating oncolytic virotherapy in a syngeneic animal model. Mol Ther 2003;7:163–173.

    Article  PubMed  CAS  Google Scholar 

  127. Soudais C, Skander N, Kremer EJ. Long-term in vivo transduction of neurons throughout the rat CNS using novel helper-dependent CAV-2 vectors. Faseb J 2004;18:391–393.

    PubMed  CAS  Google Scholar 

  128. Renaut L, Colin M, Leite JP, Benko M, D’Halluin JC. Abolition of hCAR-dependent cell tropism using fiber knobs of Atadenovirus serotypes. Virology 2004;321:189–204.

    Article  PubMed  CAS  Google Scholar 

  129. Wu Q, Tikoo SK. Altered tropism of recombinant bovine adenovirus type-3 expressing chimeric fiber. Virus Res 2004;99:9–15.

    Article  PubMed  CAS  Google Scholar 

  130. Cohen CJ, Xiang ZQ, Gao GP, Ertl HC, Wilson JM, Bergelson JM. Chimpanzee adenovirus CV-68 adapted as a gene delivery vector interacts with the coxsackievirus and adenovirus receptor. J Gen Virol 2002;83:151–155.

    PubMed  CAS  Google Scholar 

  131. Zhang Y, Chirmule N, Gao GP, et al. Acute cytokine response to systemic adenoviral vectors in mice is mediated by dendritic cells and macrophages. Mol Ther 2001;3:697–707.

    Article  PubMed  CAS  Google Scholar 

  132. Muruve DA, Barnes MJ, Stillman IE, Libermann TA. Adenoviral gene therapy leads to rapid induction of multiple chemokines and acute neutrophil-dependent hepatic injury in vivo. Hum Gene Ther 1999; 10:965–976.

    Article  PubMed  CAS  Google Scholar 

  133. Reid T, Galanis E, Abbruzzese J, et al. Intra-arterial administration of a replication-selective adenovirus (dl1520) in patients with colorectal carcinoma metastatic to the liver: a phase I trial. Gene Ther 2001;8:1618–1626.

    Article  PubMed  CAS  Google Scholar 

  134. Crystal RG, Harvey BG, Wisnivesky JP, et al. Analysis of risk factors for local delivery of low-and intermediate-dose adenovirus gene transfer vectors to individuals with a spectrum of comorbid conditions. Hum Gene Ther 2002; 13:65–100.

    Article  PubMed  CAS  Google Scholar 

  135. Ben-Gary H, McKinney RL, Rosengart T, Lesser ML, Crystal RG. Systemic interleukin-6 responses following administration of adenovirus gene transfer vectors to humans by different routes. Mol Ther 2002; 6:287–297.

    Article  PubMed  CAS  Google Scholar 

  136. Mickelson CA. Department of Health and Human Services National Institutes of Health Recombinant DNA Advisory Committee. Minutes of meeting March 8–10, 2000. Hum Gene Ther 2000; 11:2159–2192.

    Article  PubMed  CAS  Google Scholar 

  137. McCoy RD, Davidson BL, Roessler BJ, et al. Pulmonary inflammation induced by incomplete or inactivated adenoviral particles. Hum Gene Ther 1995;6:1553–1560.

    Article  PubMed  CAS  Google Scholar 

  138. Liu Q, Zaiss AK, Colarusso P, et al. The role of capsid-endothelial interactions in the innate immune response to adenovirus vectors. Hum Gene Ther 2003; 14:627–643.

    Article  PubMed  CAS  Google Scholar 

  139. Toietta G MV, Pastore L, Finegold MJ, Ng P, Beaudet AL, Lee B. Determinants of and pharmacologic modulation of acute toxicity associated with systemic administration of first feneration and helper-dependent adenovirus vectors. Mol. Therapy 2003;7:S162.

    Google Scholar 

  140. Smith TA, Idamakanti N, Marshall-Neff J, et al. Receptor interactions involved in adenoviral-mediated gene delivery after systemic administration in non-human primates. Hum Gene Ther 2003; 14:1595–1604.

    Article  PubMed  CAS  Google Scholar 

  141. George JS. Gene therapy progress and prospects: adenoviral vectors. GeneTher 2003;10:1135–1141.

    Google Scholar 

  142. Ginsberg HS, Moldawer LL, Sehgal PB, et al. A mouse model for investigating the molecular pathogenesis of adenovirus pneumonia. Proc Natl Acad Sci U S A 1991;88:1651–1655.

    Article  PubMed  CAS  Google Scholar 

  143. Wang Y, Hallden G, Hill R, et al. E3 gene manipulations affect oncolytic adenovirus activity in immunocompetent tumor models. Nat Biotechnol 2003;21:1328–1335.

    Article  PubMed  CAS  Google Scholar 

  144. Nemunaitis J, Ganly I, Khuri F, et al. Selective replication and oncolysis in p53 mutant tumors with ONYX-015, an E1B-55kD gene-deleted adenovirus, in patients with advanced head and neck cancer: a phase II trial. Cancer Res 2000;60:6359–6366.

    PubMed  CAS  Google Scholar 

  145. Shayakhmetov DM, Li ZY, Ni S, Lieber A. Interference with the IL-1 signaling pathway improves the toxicity profile of systemically applied adenovirus vectors. J Immunol 2005; 174:7310–7319.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA

    Dmitry M. Shayakhmetov PhD

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  1. Dmitry M. Shayakhmetov PhD
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  1. The University of Texas M. D. Anderson Cancer Center, Houston, TX

    Kelly K. Hunt MD  & Stephen G. Swisher MD  & 

  2. Inselspital Bern, University of Bern, Bern, Switzerland

    Stephan A. Vorburger MD, MCR

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Shayakhmetov, D.M. (2007). Efficacy, Toxicity, and Immunogenicity of Adenoviral Vectors. In: Hunt, K.K., Vorburger, S.A., Swisher, S.G. (eds) Gene Therapy for Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-222-9_2

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  • DOI: https://doi.org/10.1007/978-1-59745-222-9_2

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