Adenovirus mediated gene therapy

S. Kaneko, P. Hallenbeck, T. Kotani, H. Nakabayashi, G. McGarrity, T. Tamaoki, W. F. Anderson, and Y. L. Chiang, Adenovirus-mediated gene therapy of hepatocellular carcinoma using cancer-specific gene expression, Cancer Res. 55 5283 (1995). 

T. Tanaka, F. Kanai, K. H. Lan, M. Ohashi, Y. Shiratori, Y. Yoshida, H. Hamada, and M. Omata, Adenovirus-mediated gene therapy of gastric carcinoma using cancer-specific gene expression in vivo, Biochem. Biophys. Res. Commun. 231 115 (1997). 

However, a variety of issues have implications for the use of viral vectors in gene therapy. Obvious potential concerns are the immune and inflammatory responses to viral vectors. Patients who received VEGF-121 via an adenoviral vector had increased levels of serum antiadenoviral neutralizing antibodies, but there was no report on an inflammatory response in these patients (27). The use of adenovirus-mediated gene therapy in treating brain tumors has been reported to lead to active brain inflammation as well as persistent (up to three months after treatment) transgene expression (30). 

Dewey RA, Morrissey G, Cowsill CM, et al. Chronic brain inflammation and persistent herpes simplex virus I thymidine kinase expression in survivors of syngeneic glioma treated by adenovirus-mediated gene therapy implications for clinical trials. Nat Med 1999 5 1256-1263. 

Matsuse T, Teramoto S (2000). Progress in adenovirus-mediated gene therapy for cystic fibrosis lung disease. Curr. Therapeu. Res. 61 422-434. 

Perez-Cruet MJ, Trask TW, Chen SH, Goodman JC, Woo SLC, Grossman RG, Shine HD. Adenovirus-mediated gene therapy of experimental gliomas. J Neurosci Res 1994 39 506-511. 

Kass-Eisler A, LeinwandL, GallJ, Bloom B, Falck-Pedersen E. Circumventing the immune response to adenovirus-mediated gene therapy. GeneTher 1996 3 154-162. 

Chen, S.H., Shine, H.D., Goodman, J.C., Grossman, R.G., Woo, S.L. (1994). Gene therapy for brain tumors regression of experimental ghomas by adenovirus-mediated gene transfer in vivo. Proc. Natl. Acad. Sci. U.S.A., 91(8), 3054-3057. 

Unlike retroviruses, adenoviruses do not integrate into the host genome and thus do not replicate. As a result, genes delivered by adenoviruses are only active temporarily. Adenoviral-mediated gene therapy is employed commonly in cancer patients because permanent gene expression is unnecessary in this patient population. 

Andrawiss M, Maron A, Beltran W, Opolon P, Connault E, Griscelli F, Yeh P, Perricaudet M, Devauchelle P. Adenovirus-mediated gene transfer in canine eyes A preclinical study for gene therapy of human uveal melanoma. J Gene Med 2001 3 228-239. 

Gustafson, J.A., Price, R.A., Greish, K. et al. (2010) SUk-elastin-like hydrogel improves the safety of adenovirus-mediated gene-directed enzyme-prodmg therapy. Molecular Pharmacology, 7, 1050-1056. 

Sen, L., Hong, Y. S., Luo, H. M., Cui, G. G., and Laks, H. 2001. Efficiency, efficacy, and adverse effects of adenovirus- vs. hposome-mediated gene therapy in cardiac allografts. American Journal of Physiology-Heart and Circulatory Physiology, 281, H1433-H1441. 

Adesanya MR, Redman RS, Baum BJ and O Connell BC (1996). Immediate inflammatory responses to adenovirus-mediated gene transfer in rat salivary glands. Human Gene Therapy, 7 1085-93. 

Chapelier A, Danel C, Mazmanian M, Bacha E A Sellak H, Gilbert M A Herve P, Lemarchand P. Gene therapy in limg transplantation feasibility of ex vivo adenovirus-mediated gene transfer to the graft. Hum Gene Therapy 1996 7 1837-1845. 

In October 2003, the SFDA approved the world s first gene therapy— Gendicine (a recombinant human adenovirus type 5 mediated delivery of p53 gene)— for the treatment of head and neck cancer. In 2005, another head and neck cancer drug, Oncorine (a recombinant oncolytic adenovirus type 5), was approved. In the same year, another recombinant human endostatin, Endostar, was approved for the treatment of small-cell lung cancer. 

Schuler M, Rochlitz C, Horowitz JA, et al. A phase I study of adenovirus-mediated wild-type p53 gene transfer inpatients with advanced non-small cell lung cancer. Human Gene Therapy 1998 9 2075-2082. 

Nielsen LL, Lipari P, Dell J, Gurnani M, Hajian G. Adenovirus-mediated p53 gene therapy and paclitaxel have synergistic efficacy in models of human head and neck. Clin Cancer Res 1998 4 835-846. 

Bouvet M, Bold RJ, Lee J, et al. Adenovirus-mediated wild-type p53 tumor suppressor gene therapy induces apoptosis and suppresses growth of human pancreatic cancer. AnnSurg Oncol 1998 5 681-688. 

D. Nafziger, J. Pegg, D. Paielli, S. Brown, K. Barton, M. Lu, E. Aguilar-Cordova, J.H. Kim, Phase I study of replication-competent adenovirus-mediated double suicide gene therapy for the treatment of locally recurrent prostate cancer. Cancer Res. 62 (2002) 4968-4976. 

There is a wide variety of vectors used to deliver DNA or oligonucleotides into mammalian cells, either in vitro or in vivo. The most common vector systems are based on viral [retroviruses (9, 10), adeno-associated virus (AAV) (11), adenovirus (12, 13), herpes simplex virus (HSV) (14)] andnonviral [cationic liposomes (15,16), polymers and receptor-mediated polylysine-DNA] complexes (17). Other viral vectors that are currently under development are based on lentiviruses (18), human cytomegalovirus (CMV) (19), Epstein-Barr virus (EBV) (20), poxviruses (21), negative-strand RNA viruses (influenza virus), alphaviruses and herpesvirus saimiri (22). Also a hybrid adenoviral/retroviral vector has successfully been used for in vivo gene transduction (23). A simplified schematic representation of basic human gene therapy methods is described in Figure 13.1. 

Sterman, D. H., Treat, J., Litzky, L. A., Amin, K. M., Coonrod, L., Molnar-Kimber, K., Recio, A., Knox, L., Wilson, J. M., Albelda, S. M. and Kaiser, L. R. (1998). 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, 1083-1092. 

Bilbao R, Gerolami R, Bralet MR et al. Transduction efficacy, antitumoral effect, and toxicity of adenovirus-mediated herpes simplex virus thymidine kinase/ ganciclovir therapy of hepatocellular carcinoma the woodchuck animal model. Cancer Gene Ther 2000 7(5) 657-662. 

---