Gene therapy vaccines

PCI has been shown to increase the biological activity of a large variety of macromolecules and other molecules that do not readily penetrate the plasma membrane (Table 1). PCI has also been shown to enhance the treatment effect of targeted therapeutic macromolecules. These results show that PCI can induce efficient light-directed delivery of macromolecules into the cytosol, indicating that PCI may have a variety of useful applications for site-specific drug delivery, e.g., in gene therapy, vaccination, and cancer treatment. PCI of BLM has recently been approved for a clinical Phase I trial, where several indications have been included. The first patients with head and neck cancer have recently been treated at... 

Biotechnology-derived products may be classified into monoclonal antibodies, gene therapy, vaccines, enzymes, and interleukins. The current major therapeutic areas for these substances are cancer or cancer-related conditions, AIDS or HIV-related disease, diabetes, human growth hormone, myocardial infarction, and inflammatory disease. 

The major target indications of biopharmaceuticals currently undergoing clinical trials include cancer, cardiovascular, and infectious diseases, the major killers within the developed world. Although in excess of 30 nucleic acid-based drugs are currently being evaluated for gene therapy, vaccines, and other applications, the majority remain in the early stages of clinical development (phase I/II) [11]. 

Future cultivation methods will resemble existing methods of microbial and virus culture. Ill-defined medium components and cells will be replaced to enhance reproducibflity in production. For bacterial and ex vivo cultivated virus, analytical advances will make monitoring the environment and nutritional status of the culture more ubiquitous. However, the major changes will be in novel product types — single-molecule subunit antigens, viras-hke particles, monoclonal antibodies, and gene-therapy vaccines, each of which will incorporate novel processes. 

Shatma S, Miller P, Stolina M, et al. Multi-component gene therapy vaccines for lung cancer effective eradication of established murine tumors in vivo with interleukin 7/herpes simplex thymidine kinase-transduced autologous tumor and ex vivo-activated dendritic cells. Gene Ther 1997 4 1361-1370. 

DNA Vaccination and Genetic Vaccination Gene-therapy Vectors... 

First clinical human gene therapy trials with polyplexes were performed using cancer vaccines based on autologous patient tumor cells. These were modified ex vivo with interleukin-2 pDNA. To obtain high level transfection rates of patient s primary tumor cells, Tf-PLL/pDNA polyplexes linked with inactivated endosomolytic adenovirus particles were applied [221]. Polymer-based in vivo human gene transfer studies were performed with PEGylated PLL polyplexes, delivering CFTR pDNA to the airway epithelium of cystic fibrosis patients [222],... 

Monoclonal antibodies for in vivo use Cytokines (e.g. interferons and interleukins) Therapeutic enzymes Thrombolytic agents Hormones Growth factors Additional miscellaneous proteins Blood Blood proteins (e.g. albumin and blood factors) Vaccines Cell- and tissue-based products Gene therapy products Antitoxins, venoms and antivenins Allenergic extracts... 

An additional consideration that may influence the protocol used is the desired duration of subsequent expression of the gene product. In most cases of genetic disease, long-term expression of the inserted gene would be required. In other instances (e.g. some forms of cancer therapy or the use of gene therapy to deliver a DNA-based vaccine), short-term expression of the gene introduced would be sufficient/desirable. 

Blankenstein, T. (Ed.) 1999. Gene Therapy, Principles and Applications. Birkhauser Verlag. Lowrie, D. 1999. DNA Vaccines. Humana Press. 

DNA plasmid-based treatment ( gene therapy ) is considered an alternative to the one based on classical chemical drugs or proteins recovered from recombinant cells. Treatment of acquired and inherent genetic diseases as well as the use of DNA for the purpose of vaccination are potential applications of plasmid DNA (pDNA). The plasmid carries information that allows protein expression in the targeted human cells as well as eukaryotic regulatory elements and specific prokaryotic sequences that control replication in the host cell, see Fig. 10. Formulation is required for ex- or in-vivo administration. Selected systems for gene expression can be viral or non-viral. 

Laube BL (2005) The expanding role of aerosols in systemic drug delivery, gene therapy, and vaccination. Respir Care 50(9) 1161-1176. 

As gene therapy and stem cell research progress, we can expect more regulatory requirements to be developed to ensure proper safeguards are implemented. Similarly, xenotransplantation and control of biopharmaceutical products will experience specihe regulatory controls as new advances are made. Exhibit 11.13 presents the FDA s current oversight on gene therapy and its cautious approach to cancer vaccine. 

Anson DS. The use of retroviral vectors for gene therapy - what are the risks A review of retroviral pathogenesis and its relevance to retroviral vector-mediated gene delivery. Genet Vaccines Ther 2004 2. 

Clinical trial methodology and guidelines for special disease-related therapeutie fields are discussed. In cooperation with other working parties, guidanee for modified-release oral and transdermal dosage forms, pharmacokinetics, and clinical investigation of new vaccines, gene therapy, and cell-cultured influenza vaeeines has been... 

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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