Recombinant adenoviral vector

J. Kuball, M. Schnler, E. Antunes-Ferreira, W. Herr, M. Neumann, E. Obenaner-Kntner, E. Westreich, C. Huber, T. Wolfel, and M. Theobald, Generating p53-specific cytotoxic T lymphocytes by recombinant adenoviral vector based vaccination in mice bnt not man. Gene Therapy, 833-843 (2002). 

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Callahan SM, Ming X, Lu SK, Brunner LJ, Croyle MA. Considerations for use of recombinant adenoviral vectors Dose effect on hepatic cytochromes P450. J Pharmacol Exp Therapeut 2005 312 492-501. 

The study of the proteome of the recombinant adenovirus type 5 vectors demonstrated an important apphcation of separation techniques in combination with MS methods in the drug discovery process. With completely sequenced adenovirus genome available, this approach provides a chemically well-dehned method of characterization of structural proteins of recombinant adenoviral vectors. The information of protein MWs, tryptic peptide mass mapping, and sequence tags of tryptic peptides derived from HPLC/MS resulted in the identification of 17 adenoviral proteins/polypeptides in the purified virion. The rapid and accurate identification of viral proteins from recombinant adenoviruses in this study is significant since it provides direct evidence of the maturation stage of adenoviruses, which is closely related to viral infectivity and efficacy in gene therapy. 

Schools G, Monica T, Ayala J, et al. A high yielding serum-free cell culture process to manufacture recombinant adenoviral vectors for gene therapy. Cytotechnologf 1998 28 81— 89. 

Tsao, Y-S, Condon R, Schaefer E, et al. (2001). Development and improvement of a serum-free suspension process for the prodnction of recombinant adenoviral vectors using HEK293 cells. Cytotechnol. 37 189-198. 

Lee DS, KimBM, Seol DW. Improved purification of recombinant adenoviral vector by metal affinity membrane chromatography. Biochem. Biophys. Res. Commun. 2009 378 640-644. 

Li Q, Kay MA, Finegold M, Stratford-Perricaudet LD, Woo SL. Assessment of recombinant adenoviral vectors for hepatic gene therapy. Hum Gen Ther 1993 4 403-409. 

Katkin JP, Husser RC, Langston C, Welty SE. Exogenous surfactant enhances the delivery of recombinant adenoviral vectors to the lung. Hum Gene Ther 1997 8(2) 171-176. 

Geutskens, S.B. et al.. Recombinant adenoviral vectors have adjuvant activity and stimulate T cell responses against tumor cells. Gene Ther., 7,1410,2000. 

Based on the extensive experience with adenoviral vectors in preclinical and clinical models, a number of investigators have attempted to develop modifications that improve the safety and efficacy of the system. The flist approach was to minimize the activation of CTLs through the development of modified recombinant adenoviral vectors. 

Mizuguchi H, Kay MA. A simple method for constructing El- and El/E4-deleted recombinant adenoviral vectors. Hum Gene Ther 1999 10 2013-2017. 

Raper SE, ChirmuleN, LeeFS, et al. Lethal systemic inflammatoiy response syndrome in a patient with partial ornithine transcarbamylase deficiency following intravascular administration of recombinant adenoviral vector. Submitted. 

Dose-related gene transfer was detected in all patients at both dose levels via immunohistochemistry using an anti-HSVfA monoclonal antibody. As in the initial Phase 1 trial, significant humoral responses to the recombinant adenoviral vector were seen in all five patients, with the development of high serum titers of total and neutralizing antiadenoviral antibodies within 15-20 days of vector instillation (41). 

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