

@inbook {510,
	title = {Esterification of cidofovir with alkoxyalkanols increases oral bioavailability and diminishes drug accumulation in kidney Safe adoptive transfer of virus-specific T-cell immunity for the treatment of systemic adenovirus infection after allogeneic stem cel},
	booktitle = {Antiviral Res},
	volume = {59},
	year = {2003},
	note = {Nihms247549 S0042-6822(10)00667-7 [pii] Virology. 2011 Jan 20;409(2):141-7. doi: 10.1016/j.virol.2010.10.020. Epub 2010 Nov 5. Ciesla, Stephanie L Trahan, Julissa Wan, W Brad Beadle, James R Aldern, Kathy A Painter, George R Hostetler, Karl Y AI29164/AI/NIAID NIH HHS/United States EY11834/EY/NEI NIH HHS/United States Research Support, U.S. Gov{\textquoteright}t, Non-P.H.S. Research Support, U.S. Gov{\textquoteright}t, P.H.S. Antiviral research S0166354203001104 [pii] Antiviral Res. 2003 Aug;59(3):163-71. Feuchtinger, Tobias Matthes-Martin, Susanne Richard, Celine Lion, Thomas Fuhrer, Monika Hamprecht, Klaus Handgretinger, Rupert Peters, Christina Schuster, Friedhelm R Beck, Robert Schumm, Michael Lotfi, Ramin Jahn, Gerhard Lang, Peter Research Support, Non-U.S. Gov{\textquoteright}t British journal of haematology BJH6108 [pii] Br J Haematol. 2006 Jul;134(1):64-76. Danthinne, X Imperiale, M J GM34902/GM/NIGMS NIH HHS/United States HL64762/HL/NHLBI NIH HHS/United States Review Gene therapy Gene Ther. 2000 Oct;7(20):1707-14.},
	pages = {163-71},
	type = {Book Section},
	address = {Netherlands England},
	abstract = {Smallpox was eradicated by vaccination in the 1970s. However, concerns have arisen about the potential use of variola virus as a biological weapon. Most of the world{\textquoteright}s population has little residual immunity because systematic vaccination against smallpox ceased in the early 1970s. Vaccination of key elements of the population against smallpox is again being considered. However, there are now large numbers of persons who cannot be safely vaccinated with the current vaccine because of AIDS, immunosuppressive drugs, and certain common skin disorders. It would be useful to have a potent orally active drug as an alternative for these persons in case of an outbreak of smallpox. Alkoxyalkyl esters of cidofovir (CDV) have been shown to be highly active and selective against poxviruses in vitro with activities several logs greater than the activity of unmodified CDV. This is due in large part to increased cellular penetration and conversion to CDV-diphosphate, the active antiviral. In this paper, the oral pharmacokinetics of 14C-labeled hexadecyloxypropyl-cidofir (HDP-CDV), octadecyloxyethyl-cidofir (ODP-CDV), and oleyloxypropyl-cidofir (OLP-CDV) are examined and oral bioavailability and tissue distribution assessed and compared with parenteral CDV. The alkoxyalkyl CDVs are highly orally bioavailable and do not concentrate in kidney, the site of the dose-limiting toxicity of CDV. Plasma and tissue drug levels are many times greater than the in vitro EC(50s) for variola, cowpox, and vaccinia viruses. Thus, the compounds are good candidates for further development for prevention and treatment of smallpox infection and the complications of vaccination. During periods of immunosuppression, such as postallogeneic stem cell transplantation (SCT), patients are at significant risk for severe viral infections. Human adenovirus (HAdV) infection is a serious complication post-SCT, especially in children. Virus-specific T cells are essential for the clearance of HAdV, as antiviral chemotherapy has revealed limited success. We present feasibility data for a new treatment option using virus-specific donor T cells for adoptive transfer of immunity to patients with HAdV-infection/reactivation. Virus-specific donor T cells were isolated and infused into nine children with systemic HAdV infection after SCT. Isolation was based on gamma-interferon (IFN-gamma) secretion after short in vitro stimulation with viral antigen, resulting in a combination of CD4(+) and CD8(+) T cells. 1.2-50 x 10(3)/kg T cells were infused for adoptive transfer. Isolated cells showed high specificity and markedly reduced alloreactivity in vitro. Adoptive transfer of HAdV-specific immunity was successful in five of six evaluable patients, documented by a dose-independent and sustained in vivo expansion of HAdV-specific T cells, associated with a durable clearance/decrease of viral copies. T-cell infusion was well tolerated in all nine patients, except one case with graft-versus-host disease II of the skin. In conclusion, induction of a specific T-cell response through adoptive transfer was feasible and effective. When performed early in the course of infection, adoptive T-cell transfer may protect from HAdV-related complications. In the past decade, adenovirus vectors have generated tremendous interest, especially in gene therapy applications. In the so-called {\textquoteright}first generation{\textquoteright} adenovirus vectors, the transgenes are inserted in place of the E1 region, or less often the E3 region. Although second-generation and helper-dependent adenovirus vectors will probably prevail in the future in applications that require long-term gene expression, first generation adenovirus vectors will remain very useful in other settings, such as cancer and vaccination, or simply to transfect cell lines that are refractory to other transfection methods. Until a few years ago, the construction of first generation adenovirus vectors was a labor-intensive and time-consuming process. More than 20 methods have appeared that facilitate their construction and are reviewed below.},
	keywords = {Administration, Genetic Transfection/methods, Homologous Treatment Outcome Adenoviridae/ genetics Gene Transfer Techniques Genetic Therapy/methods Genetic Vectors Recombination, Human/ immunology Adoptive Transfer/ methods CD4-Positive T-Lymphocytes/immunology/virology CD8-Positive T-Lymphocytes/immunology/virology Cell Proliferation Cell Separation/methods Child Child, Human/immunology/ therapy Adenoviruses, Oral Animals Antiviral Agents/administration \& dosage/ chemistry/ pharmacokinetics Biological Availability Carbon Radioisotopes/pharmacokinetics Cytosine/administration \& dosage/ analogs \& derivatives/ chemistry/ pharmacokinetics Esterification Esters/ch, Preschool Feasibility Studies Hematopoietic Stem Cell Transplantation/ adverse effects Humans Infant T-Lymphocytes/immunology/ virology Transplantation},
	isbn = {0166-3542 (Print) 0166-3542 (Linking) 0007-1048 (Print) 0007-1048 (Linking) 0969-7128 (Print) 0969-7128 (Linking)},
	doi = {10.1016/j.virol.2010.10.020 10.1111/j.1365-2141.2006.06108.x 10.1038/sj.gt.3301301},
	author = {Ciesla, S. L. and Trahan, J. and Wan, W. B. and Beadle, J. R. and Aldern, K. A. and Painter, G. R. and Hostetler, K. Y. and Feuchtinger, T. and Matthes-Martin, S. and Richard, C. and Lion, T. and Fuhrer, M. and Hamprecht, K. and Handgretinger, R. and Peters, C. and Schuster, F. R. and Beck, R. and Schumm, M. and Lotfi, R. and Jahn, G. and Lang, P. and Danthinne, X. and Imperiale, M. J.}
}
